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The fascinating science behind the first human HIV mRNA vaccine trial – what exactly does it entail?

In a moment described as a “potential first step forward” in protecting people against one of the world’s most devastating pandemics, Moderna, International AIDS Vaccine Initiative (IAVI), and the Bill and Melinda Gates Foundation have joined forces to begin a landmark trial — the first human trials of an HIV vaccine based on messenger ribonucleic acid (mRNA) technology. The collaboration between these organizations, a mixture of non-profits and a company, will bring plenty of experience and technology to the table, which is absolutely necessary when taking on this type of mammoth challenge.

The goal is more than worth it: helping the estimated 37.7 million people currently living with HIV (including 1.7 million children) and protecting those who will be exposed to the virus in the future. Sadly, around 16% of the infected population (6.1 million people) are unaware they are carriers.

Despite progress, HIV remains lethal. Disturbingly, in 2020, 680,000 people died of AIDS-related illnesses, despite inroads made in therapies to dampen the disease’s effects on the immune system. One of these, antiretroviral therapy (ART), has proven to be highly effective in preventing HIV transmission, clinical progression, and death. Still, even with the success of this lifelong therapy, the number of HIV-infected individuals continues to grow.

There is no cure for this disease. Therefore, the development of vaccines to either treat HIV or prevent the acquisition of the disease would be crucial in turning the tables on the virus.

However, it’s not so easy to make an HIV vaccine because the virus mutates very quickly, creating multiple variants within the body, which produce too many targets for one therapy to treat. Plus, this highly conserved retrovirus becomes part of the human genome a mere 72 hours after transmission, meaning that high levels of neutralizing antibodies must be present at the time of transmission to prevent infection.

Because the virus is so tricky, researchers generally consider that a therapeutic vaccine (administered after infection) is unfeasible. Instead, researchers are concentrating on a preventative or ‘prophylactic’ mRNA vaccine similar to those used by Pfizer/BioNTech and Moderna to fight COVID-19.

What is the science behind the vaccine?

The groundwork research was made possible by the discovery of broadly neutralizing HIV-1 antibodies (bnAbs) in 1990. They are the most potent human antibodies ever identified and are extremely rare, only developing in some patients with chronic HIV after years of infection.

Significantly, bnAbs can neutralize the particular viral strain infecting that patient and other variants of HIV–hence, the term ‘broad’ in broadly neutralizing antibodies. They achieve this by using unusual extensions not seen in other immune cells to penetrate the HIV envelope glycoprotein (Env). The Env is the virus’s outer shell, formed from the cell membrane of the host cell it has invaded, making it extremely difficult to destroy; still, bnAbs can target vulnerable sites on this shell to neutralize and eliminate infected cells.

Unfortunately, the antibodies do little to help chronic patients because there’s already too much virus in their systems; however, researchers theorize if an HIV-free person could produce bnABS, it might help protect them from infection.

Last year, the same organizations tested a vaccine based on this idea in extensive animal tests and a small human trial that didn’t employ mRNA technology. It showed that specific immunogens—substances that can provoke an immune response—triggered the desired antibodies in dozens of people participating in the research. “This study demonstrates proof of principle for a new vaccine concept for HIV,” said Professor William Schief, Department of Immunology and Microbiology at Scripps Research, who worked on the previous trial.

BnABS are the desired endgame with the potential HIV mRNA vaccine and the fundamental basis of its action. “The induction of bnAbs is widely considered to be a goal of HIV vaccination, and this is the first step in that process,” Moderna and the IAVI (International AIDS Vaccine Initiative) said in a statement.

So how exactly does the mRNA vaccine work?

The experimental HIV vaccine delivers coded mRNA instructions for two HIV proteins into the host’s cells: the immunogens are Env and Gag, which make up roughly 50% of the total virus particle. As a result, this triggers an immune response allowing the body to create the necessary defenses—antibodies and numerous white blood cells such as B cells and T cells—which then protect against the actual infection.

Later, the participants will also receive a booster immunogen containing Gag and Env mRNA from two other HIV strains to broaden the immune response, hopefully inducing bnABS.

Karie Youngdahl, a spokesperson for IAVI, clarified that the main aim of the vaccines is to stimulate “B cells that have the potential to produce bnAbs.” These then target the virus’s envelope—its outermost layer that protects its genetic material—to keep it from entering cells and infecting them.  

Pulling back, the team is adamant that the trial is still in the very early stages, with the volunteers possibly needing an unknown number of boosters.

“Further immunogens will be needed to guide the immune system on this path, but this prime-boost combination could be the first key element of an eventual HIV immunization regimen,” said Professor David Diemert, clinical director at George Washington University and a lead investigator in the trials.

What will happen in the Moderna HIV vaccine trial?

The Phase 1 trial consists of 56 healthy adults who are HIV negative to evaluate the safety and efficacy of vaccine candidates mRNA-1644 and mRNA-1644v2-Core. Moderna will explore how to deliver their proprietary EOD-GT8 60mer immunogen with mRNA technology and investigate how to use it to direct B cells to make proteins that elicit bnABS with the expert aid of non-profit organizations. But readers should note that only one in every 300,000 B cells in the human body produces them to give an idea of the fragility of the probability involved here.

Sensibly, the trial isn’t ‘blind,’ which means everyone who receives the vaccine will know what they’re getting at this early stage. That’s because the scientists aren’t trying to work out how well the vaccine works in this first phase lasting approximately ten months – they want to make sure it’s safe and capable of mounting the desired immune response.

And even though there is much hype around this trial, experts caution that “Moderna are testing a complicated concept which starts the immune response against HIV,” says Robin Shattock, an immunologist at Imperial College London, to the Independent. “It gets you to first base, but it’s not a home run. Essentially, we recognize that you need a series of vaccines to induce a response that gives you the breadth needed to neutralize HIV. The mRNA technology may be key to solving the HIV vaccine issue, but it’s going to be a multi-year process.”

And after this long period, if the vaccine is found to be safe and shows signs of producing an immune response, it will progress to more extensive real-world studies and a possible solution to a virus that is still decimating whole communities.

Still, this hybrid collaboration offers future hope regarding the prioritization of humans over financial gain in clinical trials – the proof is that most HIV patients are citizens of the third world.

As IAVI president Mark Feinberg wrote in June at the 40th anniversary of the HIV epidemic: “The only real hope we have of ending the HIV/AIDS pandemic is through the deployment of an effective HIV vaccine, one that is achieved through the work of partners, advocates, and community members joining hands to do together what no one individual or group can do on its own.”

Whatever the outcome, money is no longer a prerogative here, and with luck, we may see more trials based on this premise very soon.

Masks made of ostrich cells make COVID-19 glow in the dark

In the two years that SARS‑CoV‑2 has ravaged across the globe, it has caused immeasurable human loss. But we as a species have been able to create monumental solutions amidst great adversity. The latest achievement involves a standard face mask that can detect COVID-19 in your breath, essentially making the pathogen visible.

A COVID-19 sample becomes apparent on a mask filter under ultraviolet light. Image credits: Kyoto Prefectural University.

Japanese researchers at Kyoto Prefectural University have created a mask that glows in the dark if COVID-19 is detected in a person’s breath or spit. They did this by coating masks with a mixture containing ostrich antibodies that react when they contact the SARS‑CoV‑2 virus. The filters are then removed from the masks and sprayed with a chemical that makes COVID-19 (if present) viewable using a smartphone or a dark light. The experts hope that their discovery could provide a low-cost home test to detect the virus.

Yasuhiro Tsukamoto, veterinary professor and president of Kyoto Prefectural University, explains the benefits of such a technology: “It’s a much faster and direct form of initial testing than getting a PCR test.”

Tsukamoto notes that it could help those infected with the virus but who show no symptoms and are unlikely to get tested — and with a patent application and plans to commercialize inspection kits and sell them in Japan and overseas within the next year, the test appears to have a bright future. However, this all hinges on large-scale testing of the mask filters and government approval for mass production. 

Remarkably, this all came with a little help from ostriches.

The ostrich immune system is one of the most potent on Earth

To make each mask, the scientists injected inactive SARS‑CoV‑2 into female ostriches, in effect vaccinating them. Scientists then extracted antibodies from the eggs the ostriches produced, as the yolk transfers immunity to the offspring – the same way a vaccinated mother conveys disease resistance to her infant through the placenta. 

An ostrich egg yolk is perfect for this job as it is nearly 24 times bigger than a chicken’s, allowing a more significant number of antibodies to form. Additionally, immune cells are also produced far more quickly in these birds—taking a mere six weeks, as opposed to chickens, where it takes twelve.

Because ostriches have an extremely efficient immune system, thought to be the strongest of any animal on the planet, they can rapidly produce antibodies to fight an enormous range of bacteria and viruses, with a 2012 study in the Brazilian Journal of Microbiology showing they could stop Staphylococcus aureus and E. coli in their tracks – experts also predict that this bird will be instrumental in fending off epidemics in the future.

Tsukamoto himself has published numerous studies using ostrich immune cells harvested from eggs to help treat a host of health conditions, from swine flu to hair loss.

Your smartphone can image COVID-19 with this simple test

The researchers started by creating a mask filter coated with a solution of the antibodies extracted from ostriches’ eggs that react with the COVID-19 spike protein. After they had a working material, a small consort of 32 volunteers wore the masks for eight hours before the team removed the filters and sprayed them with a chemical that caused COVID-19 to glow in the dark. Scientists repeated this for ten days. Masks worn by participants infected with the virus glowed around the nose and mouth when scientists shone a dark light on them.

In a promising turn, the researchers found they could also use a smartphone LED light to detect the virus, which would considerably widen the scope of testing across the globe due to its ease of use. Essentially, it means that the material could be used to the fullest in a day-to-day setting without any additional equipment.

“We also succeeded in visualizing the virus antigen on the ostrich antibody-carrying filter when using the LED ultraviolet black light and the LED light of the smartphone as the light source. This makes it easy to use on the mask even at home.”

To further illustrate the practicability of the test, Tsukamoto told the Kyodo news agency he discovered he was infected with the virus after he wore one of the diagnostic masks. The diagnosis was also confirmed using a laboratory test, after which authorities quarantined him at a hotel.

Next, the team aims to expand the trial to 150 participants and develop the masks to glow automatically without special lighting. Dr. Tsukamoto concludes: “We can mass-produce antibodies from ostriches at a low cost. In the future, I want to make this into an easy testing kit that anyone can use.”

Researchers found intact, 2,000-year-old brain cells turned to glass after the eruption of Mount Vesuvius

Italian researchers report finding intact brain cells in the skull of a man who died 2,000 years ago in the shadow of Mount Vesuvius.

Fragments of glassy black material extracted from the ancient skull. Image credits Pierpaolo Petrone et al., (2020), N Engl J Med.

The eruption of Mount Vesuvius, which destroyed the Roman city of Pompeii in the year 79 AD, is perhaps one of the widest-known events of its kind in history. However, Pompeii was not the only city that was claimed by the ashes on that day — Herculaneum, Oplontis, Stabiae, and other smaller settlements suffered the same fate.

New investigations on the remains of a young man discovered during digs in Herculaneum in the 1960s found that some of his brain cells were still intact, despite being thousands of years old.

Keep your head in the game

“The brain exposed to the hot volcanic ash must first have liquefied and then immediately turned into a glassy material by the rapid cooling of the volcanic ash deposit,” explains Pier Paolo Petrone, a forensic anthropologist at the University of Naples Federico II who led the research.

“[The cells in his spinal cord were preserved] incredibly well preserved with a resolution that is impossible to find anywhere else.”

The remains were found face-down on a wooden bed and he was likely around 25 at the time of his death, according to the team. The investigations were prompted by one researcher noticing “some glassy material shining from within the skull” in 2008.

That shiny material was the result of the vitrification (the process of something turning into glass, or becoming glass-like) of the young man’s brain during the eruption. Vitrification is the process used to create ceramics or glass from raw materials, and involves high heat and rapid cooling which alters a material’s molecular structure.

Despite the fact that this process was probably quick and very intense, brain cells in the individual’s spinal cord maintained their shape and position. In effect, they became excellent, glassy fossils. Guido Giordano, a volcanologist at Roma Tre University and co-author of the study called it a “perfect” preservation and a “totally unprecedented” finding in a vitrified specimen.

“This opens up the room for studies of these ancient people that have never been possible,” he added.

Charred wood found next to the victim allowed the team to estimate that it experienced temperatures of more than 500 degrees Celsius (932 degrees Fahrenheit). The skeleton was found inside the city’s college of the Augustales, a temple dedicated to the Roman Emperor Augustus who was the first to be worshipped as a god.

The team will continue to study the remains and try to understand what conditions are needed to create such spectacular vitrification. They also hope to isolate and analyze proteins from the remains, perhaps even genetic material.

The paper “Heat-Induced Brain Vitrification from the Vesuvius Eruption in c.e. 79” has been published in the New England Journal of Medicine.

Our white blood cells could be ‘reprogrammed’ to lower inflammation on demand

White blood cells receive ‘orders’ from our bodies to cause or subdue inflammation, a new paper reports, as a natural part of the immune response.

A mouse macrophage engulfing two particles at the same time (unrelated to the study).
Image via Wikimedia.

They argue that this effect can be used to prevent Acute Respiratory Distress Syndrome (ARDS), which affects some COVID-19 patients. ARDS is a type of respiratory failure caused by a buildup of fluid in the lungs.

Pimp my immune response

“We found that macrophage programming is driven by more than the immune system — it is also driven by the environment in which the macrophages reside,” said lead author Asrar Malik, the Schweppe Family Distinguished Professor and head of pharmacology and regenerative medicine at the University of Illinois at Chicago (UIC).

Macrophages are those immune cells that find a threat, wrap around it, and start digesting it. However, the new findings showcase that they also play a part in controlling inflammation. While a natural part of our bodies’ efforts against infection, and quite effective against them, excessive or prolonged inflammation can also damage our own tissues and organs.

In essence, these cells both cause and keep inflammation in check. The team analyzed how they determine which of the two approaches they use at any given time using mice. Their goal was to help patients suffering from excessive inflammation and conditions such as ARDS while infected with the coronavirus.

“We demonstrated that lung endothelial cells — which are the cells that line blood vessels — are essential in programming macrophages with potent tissue-reparative and anti-inflammatory functions,” said Dr. Jalees Rehman, UIC professor of medicine and pharmacology and regenerative medicine and co-lead author of the paper.

The researchers found that one protein, R-spondin-3, was present in high levels in the blood during injury and inflammation. The next step was to genetically-engineer lab mice to lack this protein in these cells — which led to the macrophages no longer dampening inflammation.

“Instead, the lungs became more injured,” said Bisheng Zhou, UIC research assistant professor of pharmacology and regenerative medicine and first author of the study. “We tried this in multiple models of inflammatory lung injury and found consistent results, suggesting that blood vessels play an important instructive role in guiding the programming of macrophages.”

The findings point the way towards a promising avenue of treatment for ARDS, but could also help us understand why some patients have better outcomes after a COVID-19 infection than others. Our own immune response has been shown to cause an important part of the damage associated with this disease. Poor vascular health or other underlying conditions that affect our blood vessels could impact our recovery, the team believes.

While the study only worked with lung tissue, it’s likely that those in other organs would show the same mechanisms, according to the authors.

The paper “The angiocrine Rspondin3 instructs interstitial macrophage transition via metabolic–epigenetic reprogramming and resolves inflammatory injury” has been published in the journal Nature Immunology.

What is osmosis — the most important principle in biology

Osmosis is a biophysical phenomenon in which water (or another solvent) moves from a less concentrated solution to a more concentrated solution through a partially permeable membrane (in other words, it lets some particles pass, while blocking others).

The solvent will maintain this migration until equilibrium in concentration is reached.

So whenever there’s a net migration of the water molecules from a solution that has a low solute concentration towards one that has a higher solute concentration, we call this phenomenon osmosis. This movement is also sometimes referred to as “down the concentration gradient”.

Osmotic pressure is the force required to prevent water movement across the semipermeable membrane.

The term osmosis, which is Greek for ‘thrust’ or ‘impulse’, was first coined by J.A. Nollet, who in 1747 described an experiment in which he used an animal bladder to separate two chambers containing water and wine. He noticed that the volume in the chamber containing wine increased and, if the chamber was closed, pressure rose.

How osmosis works

A classic experiment for osmosis involves splitting a beaker of water into two halves, with a semipermeable membrane in between and salt added to one of the sides. You’ll soon notice water migrating from the side of the beaker with no salt at all to the side with the saline solution. This movement of water will continue until the concentration of salt is the same on both sides.

It’s the same reason why you should never put a snail near salt, which would cause the poor creature to die as its water is extracted.

Key to osmosis is the presence of a semipermeable membrane that makes it more likely for water molecules in a low concentration solution to collide with the membrane and pass through, whereas water molecules in a concentrated solution will have far fewer molecules of water colliding with the membrane and passing through. This mismatch means that there’s a greater statistical probability of more water molecules passing through the membrane from a less concentrated solution. Once the statistical probability of water molecules passing through the membrane is equal, osmosis stops.

Osmosis in nature

Osmosis is one of the essential processes of life. Each cell of our body, plants, and animals around us owe their survival to osmosis.

Take plants, for instance. When we water them, we pour it on the stem end and soil. If the plant’s cells are surrounded by a solution that contains a higher concentration of water molecules than the solution inside the cells, water will enter the leaves, fruits, and flowers by osmosis. During this process, the plant cell will become firm.

However, if a plant is surrounded by a solution that contains a lower concentration of water, then the water molecules of the solution inside the plant’s cells will be expelled by osmosis, turning the plant flaccid.

When we water plants, we usually water the stem end and soil in which they are growing. Hence, the roots of the plants absorb water and from the roots, water travels to different parts of the plants; be it leaves, fruits or flowers. Every root acts as a semipermeable barrier, which allows water molecules to transfer from high concentration (soil) to low concentration (roots). Roots have hair, which increases surface area and hence the water intake by the plants.

Perhaps a more relatable example is within our own bodies. When we drink water, cells absorb it by osmosis just like plant roots. The cell wall acts as a semipermeable membrane, creating osmotic pressure between the inside and outside of the cell. Blood is a more dilute solution than the cell’s cytoplasm, so water will cross through the cell wall. The same applies for nutrients and minerals, which are also transferred by osmosis.

Humans have recognized the potential of osmosis since antiquity, employing it to preserve foods. The ancients observed that adding salt or sugar removes water from tissues. At the time, the process was called imbibition due to the fact that solutes like salt and sugar attracted the water from the material they touched.

What’s the difference between osmosis and diffusion

Diffusion and osmosis are both passive transport processes, meaning they require no energy input to move substances. Both processes are essential to the proper functioning of biological processes such as the transport of water or nutrients between cells.

The main difference between the two is that diffusion can occur in any mixture, even when two solutions aren’t separated by a semipermeable membrane, whereas osmosis exclusively occurs across a semipermeable membrane.

Diffusion makes air composition uniform by redistributing chemical species, such as oxygen in the air, until equilibrium is reached: in other words, until the concentration gradient — the difference in concentration between two areas — has been eliminated. If the concentration of a species is not initially uniform, over time, diffusion will cause a mass transfer in favor of a more uniform concentration.

Bottom line: osmosis — the natural movement of water into a solution through a semipermeable membrane — is central to all of biology. It is a passive transport process like diffusion, but the two are distinct.

Researchers successfully reverse aging — in a lab dish

Researchers at the Stanford University School of Medicine have successfully de-aged human cells in a lab dish.

Image via Pixabay.

Carefully exposing human cells to Yamanaka factors, proteins involved in embryonic development that are used to transform adult cells into induced pluripotent stem (or iPS) cells, can reverse cellular aging. The authors report that old human cells in a lab dish treated with these proteins were nearly indistinguishable from fresh cells.


“We are very excited about these findings,” said study co-author Thomas Rando, MD, Ph.D., the director of Stanford’s Glenn Center for the Biology of Aging. “My colleagues and I have been pursuing the rejuvenation of tissues since our studies in the early 2000s revealed that systemic factors can make old tissues younger.”

The authors explain that iPS cells produced from adult cells become “youthful” in the process. They wondered whether the process could be stopped mid-way, in order to make the cells more vigorous without causing them to revert back to a stem state. They found that it is possible, but the procedure hinges on carefully controlling the duration of exposure to Yamanaka factors. The team can use their approach to “promote rejuvenation in multiple human cell types,” explains Vittorio Sebastiano, Ph.D. the senior author of the study.

The factors gradually wipe a cell’s genetic material clean of the bits that differentiate them — those that make a skin cell and a blood cell different, for example — and revert them back to a younger state over the course of weeks. Instead, the team only allowed exposure to continue for a few days. They then compared the genetic activity of these cells with untreated cells from both elderly adults and younger participants.

The treated cells showed signs of age reversal after four days of exposure, the team explains, and their patterns of gene expression were similar to those seen in cells from younger participants. Treated cells appeared to be about one-and-a-half to three-and-a-half years younger on average than untreated cells from elderly people. The maximum values were three and a half years for skin cells and seven and a half years for cells lining blood vessels (when comparing methylation levels, a hallmark of cell aging).

“We saw a dramatic rejuvenation across all hallmarks but one in all the cell types tested,” Sebastiano said. “But our last and most important experiment was done on muscle stem cells. Although they are naturally endowed with the ability to self-renew, this capacity wanes with age. We wondered, Can we also rejuvenate stem cells and have a long-term effect?”

The team transplanted treated muscle cells back into old mice, and reported that they regained muscle strength comparable to that of younger mice. The process also helped cells from the cartilage of people (with and without osteoarthritis) reduce the secretion of inflammatory molecules, improve cellular function, and the cells’ ability to divide.

“Although much more work needs to be done, we are hopeful that we may one day have the opportunity to reboot entire tissues,” Sebastiano said. “But first we want to make sure that this is rigorously tested in the lab and found to be safe.”

Researchers reprogram cells to build artificial structures

Researchers at Stanford have figured out a way to reprogram cells to build synthetic structures for various uses inside the body using synthetic materials.

Image credits Jia Liu et al., (2020), Biotech.

The research is based on a new technique developed by the team, which they call genetically targeted chemical assembly, or GTCA. Through the use of GTCA, they were able to construct artificial structures in mammalian and C. elegans (a worm used as a model organism) neurons out of two biocompatible materials — an insulator and a conductor.

New build order

“We turned cells into chemical engineers of a sort, that use materials we provide to construct functional polymers that change their behaviors in specific ways,” said Karl Deisseroth, professor of bioengineering and of psychiatry and behavioral sciences, who co-led the work.

“We’ve developed a technology platform that can tap into the biochemical processes of cells throughout the body,” says study co-leader Zhenan Bao.

The team focused on brain cells or neurons, but they are confident that GTCA will work on other types of cells as well.

They began by genetically modifying the cells, using standard bioengineering techniques to insert the genes encoding the enzyme APEX2 into specific neurons. The next step involved submerging the worms and tissues in a solution of diluted hydrogen peroxide and particles of the two materials that the cells would employ.

The hydrogen peroxide was needed as it triggers a series of chemical reactions in cells with the APEX2 gene that polymerizes — ties together — the particles of raw material. The end products were mesh-like weaves wound around the cells that were either conductive or insulating. Depending on the electrical properties of this mesh, the neurons’ activity was amplified (they ‘fired’ signals more often) or dampened (making them fire more slowly). The team ran the experiment with slices of living mouse brain and on cultures of neurons (also harvested from rat brains) and, after testing the properties of the polymer meshes, they also tested to see if the solution was toxic to the cells upon being injected — it wasn’t.

The team doesn’t have medical applications in mind for their research so far, saying instead that it is a “tool for exploration”. However, the findings could have massive implications for the study of multiple sclerosis, a debilitating condition that stems from the breakdown of (myelin) insulation around neurons. Conductive polymer meshes may also help in the treatment of conditions such as epilepsy, but it’s still too early to tell.

In the future, the team plans to expand on the range of materials that can be used with their method and improve the “possibilities [of] this new interface of chemistry and biology,”

The paper “Genetically targeted chemical assembly of functional materials in living cells, tissues, and animals” has been published in the journal Science.

Researchers map the molecular structure of wood in bid to make it more resilient

The molecular structure of wood is what gives the material its strength and flexibility — and new research is uncovering its secrets.

New research from the Cambridge University’s Department of Biochemistry aims to understand what makes wood strong so that we know how to make it even stronger. The team hopes that their findings can guide future forestry breeding programs towards producing stronger wood than ever before — and support the renewed interest wood is receiving as an alternative building material to steel and concrete.

Wooden it be nice?

“It is the molecular architecture of wood that determines its strength, but until now we didn’t know the precise molecular arrangement of cylindrical structures called macrofibrils in the wood cells” says Dr Jan Lyczakowski, the paper’s first author from Cambridge University’s Department of Biochemistry.

“This new technique has allowed us to see the composition of the macrofibrils, and how the molecular arrangement differs between plants, and it helps us understand how this might impact on wood density and strength.”

While there is a will, we’re still lacking a way — wood simply has inferior mechanical properties to the materials we want to replace. Its main limitation comes in regards to the load bearing superstructures of major buildings. Here, wood simply can’t perform the task: it bends, and it breaks.

However, the team believes that the fault doesn’t lie with the material itself, but rather in our limited understanding of the precise structure of wood cells.

Wood is strong because each cell that makes it up is surrounded by a thick, hardy wall. This ‘secondary wall’ is constructed out of a mix of polymers, cellulose, hemicellulose, further reinforced with lignin. The team, which also included members from Cambridge University’s Sainsbury Laboratory (SLCU) used low-temperature scanning electron microscopy (cryo-SEM) to look at the nanoscale architecture of living tree cell walls. They were looking at the microscopic details of macrofibrils in the secondary wall, which are long molecules 1000 times narrower than the width of a human hair.

They collected samples from spruce, gingko, and poplar trees in the Cambridge University Botanic Garden. Each sample was flash-frozen to keep the cells in a life-like state, and then coated in a platinum film three nanometers thick to be viewable under the electron microscope.

“Our cryo-SEM is a significant advance over previously used techniques and has allowed us to image hydrated wood cells for the first time,” said Dr Raymond Wightman, Microscopy Core Facility Manager at SLCU.

“It has revealed that there are macrofibril structures with a diameter exceeding 10 nanometres in both softwood and hardwood species, and confirmed they are common across all trees studied.”

The researchers also looked at the secondary cell walls of thale cress (Arabidopsis thaliana), a plant that is used as a model organism in genetics and molecular biology research — the plant also showed the same macrofibril structures. Using several of these plants, each showing different mutations relating to the secondary cell wall and its formation, the team was also able to identify the role of specific molecules in the development of the macrofibrils. Based on their results, the team recommends thale cress as a suitable model for future forestry breeding programmes.

“Visualising the molecular architecture of wood allows us to investigate how changing the arrangement of certain polymers within it might alter its strength,” said Professor Paul Dupree, a co-author of the study in Cambridge’s Department of Biochemistry.

“Understanding how the components of wood come together to make super strong structures is important for understanding both how plants mature, and for new materials design.”

“If we can increase the strength of wood, we may start seeing more major constructions moving away from steel and concrete to timber.”

The paper “Structural Imaging of Native Cryo-Preserved Secondary Cell Walls Reveals the Presence of Macrofibrils and Their Formation Requires Normal Cellulose, Lignin and Xylan Biosynthesis” has been published in the journal Frontiers in Plant Science.

Mitochondria and Tesla battery packs work pretty much the same way, study reports

Mitochondria are built up of many individual bioelectric units that generate energy as an array — pretty much like a Tesla electric car battery.

Mitochondria (red) are organelles found in most cells. They generate a cell’s chemical energy. Image credits NICHD / U. Manor via NICHD / Flickr.

The prevailing theory up to now was that mitochondria, the organelles that produce energy for living cells, worked like one of the batteries in your remote: though a chemical reaction inside a single chamber or battery cell.

However, a new study from the University of California, Los Angeles (ULCA) finds that this isn’t the case. Mitochondria, they explain, work like arrays, with many, many battery cells that work to manage energy safely and provide fast access to high-intensity current.

Team effort

“Nobody had looked at this before because we were so locked into this way of thinking; the assumption was that one mitochondrion meant one battery,” said Dr. Orian Shirihai, a professor of medicine in endocrinology and pharmacology at the David Geffen School of Medicine at UCLA and senior author of the study.

All cells in our bodies, with the exception of red blood cells, contain one or more mitochondria — sometimes up to several thousands of them. These organelles (cellular organs) are covered in a smooth outer membrane and boast a wrinkled, inner membrane. The folds of this inner membrane (called ‘cristae’) extend all the way to the center of the organelle.

Up to now, it was assumed that the role of this wrinkly texture on the inner membrane was simply to increase the surface area and thus help increase the energy output.

However, the world works in mysterious ways; California has taken a leading role in renewable energy and e-vehicles, and that decision made the current study possible.

“Electric vehicle engineers told me about advantages of having many small battery cells instead of one large one; if something happens to one cell, the system can keep working, and multiple small batteries can provide a very high current when you need it,” Shirihai said.

Tesla vehicles are some of the best-known e-vehicles right now, so let’s take that as an example. Tesla battery packs are an array of 5,000 to 7,000 small battery cells (depending on the exact model). These batteries, while individually small, work in tandem to allow vehicles to charge rapidly, cool down more effectively, and to provide large amounts of power quickly when needed (such as when accelerating).

Using conventional microscopy, Shirihai observed that cells can function well with a small number of very long mitochondria, which didn’t fit in with what the engineers were telling him. So, instead, he started looking for the array inside individual mitochondria. Together with his colleagues, he developed a technique to map the voltage on the membrane of mitochondria in living cells with much better accuracy than ever before. Dane Wolf (first author) and Mayuko Segawa (second author), two UCLA students, optimized a form of high-resolution microscopy to peer into the interior of mitochondria and watch energy production and voltage distribution inside the organelle.

“What the images told us was that each of these cristae is electrically independent, functioning as an autonomous battery,” Shirihai said. “One cristae can get damaged and stop functioning while the others maintain their membrane potential.”

The inner membrane of the mitochondria loops back outward between each cristae, the team reports, and clusters of proteins form in this area and determine the boundaries of individual cristae. Previous research has shown that without these proteins, the mitochondria are more susceptible to damage, but not why; Shirihai’s study found why.

These proteins, the study explains, act as insulators between cristae. In effect, they turn a huge battery into a collection of smaller ones. If these proteins disappear, the mitochondria stop acting like battery arrays.

“The battery experts I had originally talked to were very excited to hear that they were right,” Shirihai said. “It turns out that mitochondria and Teslas, with their many small batteries, are a case of convergent evolution.”

The findings may help broaden our understanding of mitochondria, the roles they play in cells and in aging, and even shed light on new treatments for diseases and medical complications that involve disturbances in mitochondria or cristae structure.

The paper “Individual cristae within the same mitochondrion display different membrane potentials and are functionally independent” has been published in The EMBO Journal.

Researchers find out how cells heat themselves

While we knew that mitochondria somehow generate heat, we didn’t exactly understand how. Researchers at the University of Illinois used a tiny thermometer to find out.

The team reports that mitochondria release heat in quick, powerful bursts using energy stored in internal proton batteries. The findings were made possible through the new tool the researchers built, as previous methods were too slow to pick up on the heat spikes.

a) False-color electron microscope image of the probe, scale bar 100 μm. c) A schematic of the experiment. d) Image of the probe in action, scale bar 100 μm.
Image credits Manjunath C. Rajagopal et al., 2019, Communications Biology.

“Producing heat is part of the mitochondria’s role in the center of metabolism activity,” said mechanical science and engineering professor Sanjiv Sinha. “It needs to produce the energy currency that’s used for the activities in the cell, and heat is one of the byproducts.”

Mitochondria also have a mechanism in place to increase heat output if needed, such as when the body’s overall temperature goes down. In order to get a better understanding of how this heat is generated, the team developed a fast-read thermometer probe measure the internal temperature of living cells. Tab of Rhanor Gillette, professor emeritus of molecular and integrative physiology at Illinois, helped test the probe in a mitochondria-rich strain of neurons.

The team then made the cells produce heat. They recorded very fast changes in temperature inside the neurons, “results that were completely different from what has been published before” according to first author Manjunath Rajagopal.

“We saw a sharp temperature spike that is significantly large and short-lived — around 5 degrees Celsius and less than one second,” he explains.

“The gold standard for measuring has been with fluorescence, but it is too slow to see this short, high burst of heat.”

The findings conflict with previous assumptions that mitochondria break down glucose to generate heat: the temperature spikes, Sinha says, are too large. In order to find the source of energy, the team turned to the mitochondria, and chemically induced them to open up protein channels on their membrane.

“In the mitochondria, one part of the glucose metabolism reaction stores some of the energy as a proton battery. It pushes all the protons to one side of a membrane, which creates an energy store,” Rajagopal said.

“We basically short-circuited the stored energy.”

In the future, the team wants to use their probe on other types of cells. One of their primary focus will be identifying therapeutic targets, they add. Better control over this energy sink could have applications against obesity and cancer.

The paper “Transient heat release during induced mitochondrial proton uncoupling” has been published in the journal Communications Biology.


Discovery of new “don’t eat me protein” points the way to effective cancer therapy

Stanford University (SU) researchers have found a new signaling molecule that cancer cells use to keep the immune system at bay.


Image via Pixabay.

Our bodies’ immune cells are, among other objectives, tasked with clearing out malfunctioning cells. In theory, cancer cells fall into this category and should be targeted; in practice, however, they use all sorts of biochemical tricks to avoid detection. Researchers at the SU School of Medicine have identified a new signaling molecule that cancer cells use for this purpose.

Cloaking proteins

Immune system cells called macrophages normally detect sick or damaged cells, then proceed to engulf and devour them. In recent years, however, researchers have discovered that proteins on the cell surface can tell macrophages not to destroy them. While this mechanism is meant for good, law-abiding cells to keep the immune system from attacking them, cancer cells have hijacked the same mechanism.

The authors’ past research has shown that the proteins PDL1 and CD47 are used by cancer cells to hide from immune system cells. The discovery of these two proteins and their role also pointed to a possible treatment against cancer: blocking them to ‘uncloak’ cancer cells. Antibodies aimed at blocking CD47 undergoing clinical trials, while treatments targeting PDL1 are already in use in oncology clinics. 

“Finding that not all patients responded to anti-CD47 antibodies helped fuel our research at Stanford to test whether non-responder cells and patients might have alternative ‘don’t eat me’ signals,” said co-author Irving Weissman, the Virginia and D.K. Ludwig Professors for Clinical Investigation in Cancer Research.

The team reports finding a new such protein, called CD24, that cancer cells employ as a “don’t eat me” sign. They began by looking for proteins that were produced in larger quantities in cancer cells than in the surrounding, healthy tissues. The hypothesis the team was working on was that cancers growing in the presence of macrophages need to produce some kind of signaling molecule to keep themselves safe. This should be reflected in a higher concentration of that particular compound in the cancer cells — and, by disrupting this compound, cancer could be made vulnerable.

Many different types of cancer produce higher levels of CD24 compared with normal cells and surrounding tissues, the team explains. They further showed that macrophage cells which infiltrate the tumor sense the presence of this protein through a specialized receptor (SIGLEC-10). They placed a mix of cancer cells harvested from patients and macrophages in a dish and then blocked the interaction between CD24 and SIGLEC-10. The macrophages immediately started breaking down the cancer cells, they explain. Lastly, they implanted human breast cancer cells in mice and blocked CD24 signaling — the mice’s macrophages attacked the cancer cells, the team reports.

Of particular interest was the discovery that ovarian and triple-negative breast cancer, both of which are very hard to treat, were highly affected by blocking the CD24 signaling.

“This may be a vulnerability for those very dangerous cancers,” said Amira Barkal, an MD-PhD student and lead author of the paper.

CD24 seems to often work as a complement to CD47 — one of the previously-identified ‘don’t eat me’ proteins — the team adds. Some cancers, like blood cancer, are highly susceptible to CD47-signaling blockage but not to CD24-signaling blockage. Others, like ovarian cancer, show the exact opposite susceptibility. This finding makes the team confident that most (if not all) types of cancers can be attacked by blocking one of these two signaling molecules.

The researchers now hope that therapies to block CD24 signaling will follow in the footsteps of anti-CD47 therapies, being tested first for safety in preclinical trials, followed by safety and efficacy clinical trials in humans. In the future, they plan to keep sniffing out such proteins in a bid to make cancers even more vulnerable by blocking several ‘don’t eat me’ proteins at a time.

“There are probably many major and minor ‘don’t eat me’ signals, and CD24 seems to be one of the major ones,” Barkal said.

Combined with novel ways of detecting the disease, such treatment avenues may finally spell the end of cancer as we know it today. Not a day too soon.

The paper “Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy” has been published in the journal Nature Immunology.


Credit: Pixabay.

New study reveals secret language of cell communication

Credit: Pixabay.

Credit: Pixabay.

Humans are complex organisms made up of trillions of cells, and each of these cells has their own structure and function. Naturally, all of these cells have to communicate with each other so that the body can properly function. Otherwise, your brain couldn’t instruct the muscles in your legs to move or there would be no way to heal when you get an injury. In a new study, researchers at the University of Connecticut have revealed new insights into the complex web of cell communication. 

While humans use words and language to communicate, cells send and receive messages or instructions by secreting proteins. But words mean very little without structure, just like language means very little without grammar. Cells also have their own conversational structure, but until recently we knew very little about it.

“This is akin to detecting what words were spoken in a sentence, but not really knowing their placement, the inflection, and tone of the message,” said Kshitiz Gupta, an assistant professor at the UConn School of Dental Medicine.

Kshitiz and colleagues employed microfluidics and computer modeling to reveal the precise wording and structure of intercellular communication. During one experiment, the researchers zoomed in on stem cells from bone marrow that can be used to treat a myocardial infarction, also known as a heart attack. The team recorded proteins that were secreted by these stem cells, as well as how these secretions changed with time.

In the lab, the researchers used this information to make a protein cocktail that could one day be used to treat an injury without the use of stem cells. While stem cells are flexible enough to change their function and behavior depending on the site of injury, it is possible to copy a particular stem cell behavior and create a cell-less therapy that only uses proteins. Such an approach could avoid some of the complications associated with stem cell transplants.

“The findings solve a fundamental problem afflicting systems biology: measuring how cells communicate with each other,” said Yashir Suhail, a postdoctoral fellow, in the Dental School’s Department of Biomedical Engineering. “The platform technology will open new lines of inquiry into research, by providing a unique way to detect how cells talk to each other at a deeper level than what is possible today.”

The findings appeared in the journal Nature Communications.

Cell image.

When faced with high gravity, cells get “thicker skin” by strengthening their membranes

When gravity increases, cells thicken their skins, new research shows.

Cell image.

Image credits Emma M. Woodcock et al., (2019), Biophysical Journal.

Researchers from the European Space Agency (ESA) and Imperial College, London report that as gravity increases, cells develop more viscous membranes to hold their shape — similar to developing a “thicker skin”. This study is the first to document the changes in cell membrane viscosity that occur at higher and extreme gravities.

Thick, thicker, thickest

“Studying how cells adapt to extreme gravity helps us understand how cells can resist environmental stress in general—from viral attacks and chemical imbalance to extreme cold and extreme heat,” says Dr. Nick Brooks, co-author of the study and Senior Lecturer in the Department of Chemistry at Imperial.

“Another really exciting thing was showing we could do it. Actually being able to conduct detailed microscopy experiments inside of a centrifuge which is spinning at 15g is not very easy.”

Using the European Space Agency’s (ESA) Large Diameter Centrifuge in the Netherlands, the team pitted living cells against a gravitational force 15 times stronger than Earth’s (i.e. 15g). As gravity increased, so did cell membrane viscosity, the team reports. These results may not sound like much, but the authors note that membrane viscosity is an important parameter for cells, as it controls how quickly some key reactions occur — and, indeed, if they can take place at all.

The findings may help us develop better treatments for diseases like diabetes and Alzheimer’s that can change the viscosity within cells. They also simply help us better understand how cells go about their routine lives.

Cells development over time.

Image credits Emma M. Woodcock et al., (2019), Biophysical Journal.

The study was led by Imperial Ph.D. graduate Emma Woodcock as part of the Spin Your Thesis! competition that gives students access to the ESA’s centrifuge — a four-armed, eight-meter in diameter spinning beast. Her study brought together Imperial chemists, physicists, and ESA scientists. At full speed, the centrifuge can spin containers at the ends of its arms at 101km/hour, roughly 60mph. Simulated gravity inside these containers can reach up to 20g. The most powerful simulated gravitational force you likely experienced was on a rollercoaster ride; to give you some context, the most powerful rollercoasters today only touch the 5g mark for a few seconds at a time.

The team made several impressive advancements for this study. They successfully secured a camera and microscope inside the containers and managed to keep them properly focused throughout the experiment. Dr. Marina Kuimova, one of the paper’s co-authors and an Associate Professor in the Department of Chemistry at Imperial also developed molecules that would light up as viscosity in the cellular membranes increased. These molecules have a spinning axis that rotates faster in low viscosity but becomes progressively stalled as the membrane stiffens. When not spinning, it emits bright fluorescent light — and the light it emits is reliable and stable enough that the team could measure it to see how fast the molecule was spinning. This method doesn’t chemically interfere with the cell in any way, making it very promising for future research of this kind.

“This technique opens a whole new way of looking at how cells work,” Dr. Kuimova explains. “We usually monitor smaller changes in viscosity under normal physiological conditions, but it was exciting to apply our technique to conditions when the cells were pushed to the extreme.”

This study worked with general mouse cells and specialized human cells of the endothelium — those that line blood vessels. Both types of cells had very fast responses in stiffness to gravity levels. The team says this suggests it is mostly a physical response caused by components in the cells’ membranes, rather than an active shift in which the cell senses changes in pressure and starts to produce a mechanical change in its membrane as a result.

The human cells saw the greatest and fastest changes, the team reports, which isn’t that surprising; endothelial cells are equipped to deal with pressure changes caused by sharp corners in vessels, plaque build-up, or shifts in heart rate and blood pressure. This effect might illustrate what cells are subjected to with arterial diseases (though that happens on a larger scale), the team writes.

In the future, the team wants to look at how the cell signals to its membrane to increase viscosity. They also want to adapt their method to study the viscosity of different parts of the cell, how this is implicated in diseases and how cell membranes control other things.

The paper “Measuring Intracellular Viscosity in Conditions of Hypergravity” has been published in the Biophysical Journal.

Zooming in on the cell– what makes animals and plants different?

Plants and animals are about as different as you can get. Plants make their own food and are stuck in one place, while animals need to find food to eat and can move around on their own. But, what makes plants and animals truly different? Each living organism is built from cells, and though plant and animal cells are very similar, there are key differences between these organisms.

What makes the deer and ferns different? Image credits: Max Pixel.

As a small high school biology recap, all cells, regardless of whether they are in plants or animals, are bound in a membrane and contain organelles that perform tasks that keep the cell going. The core organelles in plant and animal cells are responsible for essential tasks such as processing energy, making new proteins, and getting rid of waste as performed by the mitochondria, endoplasmic reticulum, the Golgi Apparatus, and others. The activities going on in these cells are coordinated by the nucleus, which also stores precious DNA. Now, on to what make plant and animal cells special.

Unique to plant cells

Plants have three main differences that distinguish them from animals. Chloroplasts allow plant to make their own food by harnessing the energy of the sun. A really long time ago (millions of years), single celled organisms evolved the ability to use solar energy to split water molecules and generate oxygen. Cells engulfed some of these photosynthetic organisms, and likely formed a symbiotic relationship with them. Now, chloroplasts are not their own organism, but an organelle that serves an important function in the cell—to make sugar to feed the cell.

A cross-section of a plant cell. Image credits: Mariana Ruiz.

Another structure that is unique to plant cells is the cell wall. It is a stiff layer outside the cell membrane. It makes the cells stronger and resistant to osmotic and mechanical stress. Importantly, it also allows to plant to build up high pressure within the cell itself. When a plant is well-watered, the storage organelle of the cell (the vacuole—to be covered next) is full and presses against the cell wall. This makes a plant appear vital and sturdy. However, if conditions aren’t so good, let’s say a dry period or negligent owner, there isn’t as much pressure against the cell wall and the plant wilts. Although the plant wilts, the cell wall maintains the structure of the leaves and stems. The cell walls are also why plants are able to have rigid structures like trunks and leaves.

Vacuoles themselves are not unique to plants — animals have them as well. However, what is unique is that plants have one (comparatively) huge vacuole in the center of their cell, while animals have several smaller vacuoles. They are fluid-filled sacs that have a number of roles, including breaking down molecules and storing nutrients and other important products in the cell. The plants use the vacuoles to control their cell size and shape.

Unique to animal cells

As previously mentioned, animals do not have a rigid cell wall like plants do. Without this constraint, animals were able to evolve many different cell types, tissues, and organs. For example, animals were able to develop nerves and muscles that led to their mobility and neurological capacities. There’s a reason why you don’t see a plant taking a jog or working on a crossword puzzle—they are unable to form these types of tissues.

Cross-section of an animal cell. Image credits: Mariana Ruiz.

Since an animal cell doesn’t have a cell wall, it needs some way to keep its shape. This is where the intermediate filaments come in. They are fibrous proteins that are constructed like a rope with many long strands of filaments twisted together to resist tension. Though plants also have a cytoskeleton composed of microtubules and microfilaments, it is generally thought that they do not have intermediate filaments.

Animal cells have special lysosomes — organelles with a very low internal pH — to break down biomolecules in the cell. Specialized plant vacuoles fulfill a similar role as lysosomes, though they are named differently. They are considered different because they lack certain enzymes and functions associated with lysosomes.

There are other minor differences between plant and animal cells, but these are the major ones that make a plant a plant and an animal an animal.


Exercise, fasting boosts cellular cleanup of defective proteins


Credit: Pixabay.

The human body is comprised of systems, which are composed of organs, which are composed of tissue, which are composed of cells. It follows that the body’s physiology is directly linked to cellular performance and health. One of the essential mechanisms that ensure cells function properly is the removal of waste proteins — and according to a new study, both exercise and fasting can boost this process.

Turbocharging waste removal

A research group at the Harvard Medical School led by Alfred Goldberg, professor of cell biology, is known for its groundbreaking work in protein-disposal systems. Previously, Goldberg’s lab showed that certain drugs can boost the levels of a molecule called cAMP, triggering a cascade of effects which lead to the removal of junk proteins. This occurs when ubiquitin molecules mark old, defective, and toxic proteins for destruction by the cell’s protein-disposal unit, known as the 26S proteasome. This process is called the ubiquitin-proteasome pathway, or the ‘kiss of death’ as some scientists poetically refer to it.

Stimulating the destruction of defective or toxic proteins is important for certain individuals where this pathway is slow. Mutated proteins are particularly threatening since their buildup can lead to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer’s. Over-stimulation can also be a problem as excessive protein removal can lead to muscle wasting in cancer patients or cause muscle atrophy.

In a new study, Goldberg and colleagues have found that the same cellular quality control can be regulated independent of drugs, through fluctuations in hormone levels triggered by exercise or fasting. Experiments were carried out with four human volunteers, in the case of exercise, and mice, in the case of fasting. The researchers found that exercise led to greater levels of cAMP, thus producing more molecular marks for protein degradation. Fasting for 12 hours produced similar effects on the protein-breakdown pathway, enhancing its activity in the muscle and liver cells of mice.

In another round of experiments, the researchers showed that an array of hormones, including glucagon (glucose stimulant), epinephrine (also known as adrenaline, which boosts muscle strength during stress), and vasopressin (the antidiuretic hormone that helps the body retain water), were involved in protein degradation.

“Our findings show that the body has a built-in mechanism for cranking up the molecular machinery responsible for waste-protein removal that is so critical for the cells’ ability to adapt to new conditions,” Goldberg said in a statement.

“This is truly a new way of looking at whether we can turn up the cellular vacuum cleaner,” Goldberg said. “We thought this would require the development of new types of molecules, but we hadn’t truly appreciated that our cells continually activate this process.”

The benefits of exercise and fasting are, by now, well documented. Even moderate amounts of daily physical activity protect the brain, heart, and other important organs, keeping the body young and the mind fresh. Meanwhile, fasting has been shown to improve cellular regeneration and increase lifespan. The new findings now suggest that exercise and fasting may reduce the risk of developing conditions associated with the accumulation of misfolded proteins. In the future, this newly identified pathway for protein degradation could be the object of novel therapies.

“The beauty and the surprise of it is that such new treatments may involve churning a natural endogenous pathway and harnessing the body’s pre-existing capacity to perform quality control,” Goldberg said.

The findings appeared in the journal PNAS.

Reticular adhesions.

New structure that keeps cells bound together discovered in human cells

Researchers at the Karolinska Institutet, Sweden, report discovering a new structure in human cells. The role of this cellular structure protein seems to be fixing cells to surrounding tissues and aiding in division, the team reports.

Reticular adhesions.

Three-dimensional projection of a cancer cell that has been rounded to undergo cell division and adheres to the substrate with reticular adhesions. Blue – Chromatin (DNA); Red – Cell’s outer shell (membrane); Green/Yellow – Reticular adhesions. The image was created using a confocal microscope.
Image credits John Lock.

Cells are round-ish, soft-ish things. So then how do they tie together to form robust tissues? Well, the secret lies in a structure that surrounds them — a net-like formation known as the extracellular matrix. Much like the mortar in between bricks, this matrix brings cells together into a coherent whole.

Still, the matrix is an exclusive place — only those with special receptor molecules (adhesion complexes) on their surface are admitted. The structure discovered by the team is one such adhesion complex.

Yet more to discover

“It’s incredibly surprising that there’s a new cell structure left to discover in 2018,” says principal investigator Staffan Strömblad, professor at the Department of Biosciences and Nutrition at the Karolinska Institutet.

“The existence of this type of adhesion complex has completely passed us by.”

The team discovered a new type of protein complex that cells use to attach to their surroundings and plays a key part in cell division. Much like other adhesion complexes, it connects the outside to the cell interior and informs the cell about its immediate environment, affecting its properties and behavior. What’s special about this one is its unique molecular composition and shape — the team christened the structure ‘reticular adhesions’ to reflect their net-like shape.

While other known adhesion complexes break down during division, reticular adhesions remain intact and attached to the cell wall during the process. This discovery could help solve the long-standing question of how cells remain attached to the matrix as they divide. The team further reports that the new structure controls where daughter cells go after division, ensuring that they occupy the right place in the overall tissue.

“Our findings raise many new and important questions about the presence and function of these structures,” says Professor Strömblad. “We believe that they’re also involved in other processes than cell division, but this remains to be discovered.”

For the study, the team looked at human cell lines using confocal microscopy and mass spectrometry. To better understand the function of reticular adhesions, they add, further research efforts will need to examine them in living organisms.

Apart from the direct scientific merits of the discovery, the biggest takeaway (for me) from this research is that nature is way more complex and complicated than we give it credit for. We shouldn’t rest on our laurels because we’ve ‘discovered everything’ — we’re nowhere near done yet.

The paper “Reticular adhesions are a distinct class of cell-matrix adhesions that mediate attachment during mitosis” has been published in the journal Nature Cell Biology.


New bio-synthetic circuits can teach old cells new tricks — such as killing cancer

New research at Caltech paves the way for programmable cells.


Image via Pixabay.

The research team has developed a biological toolkit of proteins which can be mixed and matched to create circuits that program new behaviors into cells. As a proof-of-concept, the team designed and built such a circuit and added it to human cells growing in culture in the lab. The mechanism is meant to detect the activation of a certain cancer-causing gene — in which case it causes the cell to self-destruct.


One goal of synthetic biology is to enable living cells to learn new tricks, ranging from relatively simple ones, such as emitting light in certain conditions, to the more complex — for example, detecting and responding to disease. The most common way of doing this is by altering a cell’s genome. However, such alterations are permanent and will be passed on by the cell to its daughters, which is undesirable in several applications.

So, a lot of effort has been spent in synthetic biology laboratories across the world to develop less-permanent solutions, says Michael Elowitz, coauthor of the new paper, a professor of biology and biological engineering, and a Howard Hughes Medical Institute investigator. Such changes should be removable, he adds, or last only a certain time; they would be administered, carry out their intended function, then allow the cell to revert to its original state. Ideally, they should also be highly targeted: instead of affecting all cells indiscriminately, they could detect when something goes wrong on the cellular level and fix it accordingly.

Led by postdoctoral fellow Xiaojing Gao and graduate student Lucy Chong, the Caltech team developed a set of protein building blocks that they hope will enable synthetic biology to shift its paradigm towards these temporary changes.

The proteins can be assembled in various combinations to produce biological circuits that can sense their environments and act if required. Just like electronic transistors can be linked to create the huge range of circuits today, the proteins can form systems that handle everything from signal processing to logical computation.

“One of the biggest challenges in biomedicine is specificity: How do you make a therapeutic that will affect only a particular type of cell? Then, how do you respond by modifying that cell in a very specific way?” says Elowitz.

“These tasks are challenging for drugs, but biological circuits could excel at them. Protein circuits can be programmed to sense many types of information, process it, and respond in different ways. In fact, the reason our cells usually work as well as they do is the incredible power of our natural biological circuitry.”

To prove that their approach works, the team constructed a biological circuit that can detect whether cells in a culture bear a cancerous gene and if so, destroy them. This circuit remained inactive when presented with healthy cells.

“This work is simply a proof of principle and we haven’t demonstrated these functions in animals yet,” Gao adds. “However, this framework could help us transition to using programmable, cell-based therapies as medicines.”

The work was enabled by the team’s efforts to engineer proteins that regulate (interact with) one another in similar ways, allowing them to act as interchangeable building blocks in the same mechanism.

The paper “Programmable protein circuits in living cells” has been published in the journal Science.

mitosis artsy.

What Are Five Stages of Mitosis?

mitosis artsy.

“Mitosis or Fusion?” artwork.
Image credits Mike Lewinski / Flickr.

Our bodies are collections of cells, all bunched up and working together to help you successfully navigate adult life. Being the ideal heap of cells, however, involves some growing and quite a lot of maintenance. If it sounds like hard work, it’s because it probably is. Luckily for us, cells have a secret ace up their sleeves: they can simply copy-paste themselves to create new, identical members. This process — called mitosis or, more colloquially, cell division — is what allows organisms to grow, develop, and heal with virtually no conscious effort.

I’m a huge fan of not making any conscious effort — so let’s all appreciate all the work our cells aren’t putting us through while we take a look at mitosis.

Readers be warned: we will be using the animal cell as a template to discuss the processes involved. There will be some differences here and there between how these and other types of cells handle mitosis.

What is mitosis?

Mitosis is one of two types of cellular division — the other being meiosis. They’re largely identical, with the key difference being that mitosis results in two daughter cells, each with the same number and type of chromosomes as their parent, while meiosis results in cells that only have half of the parent’s chromosomes. Mitosis is how regular cells — the ones that make up your tissues, your pet’s tissues, or the yeast that fermented your beer — multiply. Meiosis is how our bodies produce sex cells, like sperm and eggs.

While it goes on without us actually doing anything (beyond staying fed and not-dead, obviously), there’s a lot of work involved in mitosis. We’ve classified the steps of this process in ‘phases’ that each cell must go through before it can divide. These are, in order:



This isn’t strictly speaking part of the meiosis process; rather, it’s more of a default-state for cells. They spend most of their lifespan in interphase, performing their usual functions and getting all stocked up on nutrients. As baby-cell-making time swings around, i.e. the later stages of interphase, cells start duplicating their internal structures — they create two copies of their DNA and of each organelle.

Interphase is generally broken down in two to three separate sub-phases:

  • Growth (G1) phase, during which the cell doubles-down on synthesizing virtually its full array of proteins, especially the structural proteins it will need to grow.
  • Synthesis (S) phase: this is when the cell’s chromosomes are duplicated.
  • [In some cases] Growth (G2) phase, which is very similar in form and function to the G1.



This is when the cell starts going into reproduction mode proper. One of the first things that happen during prophase is that the cell’s (now double-helping of) DNA condenses into pairs of chromosomes. Think of it like archiving a folder on your computer — all the information is still there, only much more compact and easier to share with your kids.

Another important event is the formation of the mitotic spindle. This starts with the cell’s centrioles — the organelles that secrete these microtubules, made from the protein that forms the spindle and cellular support skeleton — moving to the poles. From there, they release microtubules, gradually pushing them towards the middle, where they’ll eventually fuse. The mitotic spindle will elongate the cell during prophase, which will come in handy during division.

Finally, the cell’s nucleolus — the largest structure inside the nucleus, which assembles ribosomes — disappears, setting the stage for the nucleus to break down.



During a brief time window called prometaphase (the “before metaphase”), the membrane around the chromosomes breaks down. This will release the chromosomes inside the cell, and they will affix to the mitotic spindle on the equatorial plane.

The spindle is there to ensure that each daughter cell will receive a full copy of the original’s DNA. It does this by pulling the chromosome pairs onto its filaments, right across the equatorial plane — an imaginary line that falls roughly along the cell’s midline. This sorts the genetic data, so to speak, ensuring that each of the new cells-to-be will get one chromosome from each pair before the cell divides. Not all microtubules stick to a chromosome — those that do are known as kinetochore microtubules. The other microtubules will span the cell and grab on to microtubules coming from the other side, to stabilize the spindle.


The mitotic spindle in a human cell showing microtubules in green, chromosomes (DNA) in blue, and kinetochores in red.

During metaphase proper, all chromosomes are drawn into place on the spindle across the equatorial plane. By this time, each chromosome’s kinetochore — a complex protein structure associated with the chromosomes that, among other things, contains a molecular motor — should be attached to microtubules from opposite spindle poles.

Eukaryotic cells go through a lot of effort to ensure genetic integrity during mitosis — else they risk their health and that of the organism. Before proceeding to the next phase, the cell has to pass the ‘spindle checkpoint’: if all chromosome pairs are on the equatorial plane, and properly aligned (one half toward each end of the spindle), the cell gives the green light. If not, it pauses the mitosis process until everything is set.



During anaphase, the ‘glue’ holding each chromosome pair together breaks down and their members get pulled to the opposite sides of the cell — by this point, each half of the mother cell harbors a complete copy of its DNA, and the actual division can begin.

The chromosomes are pulled by kinetochore microtubules, which start to shorten towards the opposing centromeres. At the same time, the structural microtubules grow, pushing at each other, elongating the cell; imagine stretching a piece of chewing gum between your fingers — that’s roughly the shape cells take during this phase. All this activity is powered by motor proteins, such as the one in the chromosomes’ kinetochores that pull them along microtubules.



By this point, the cell is nearly done dividing, hurray!

Since cells are really a tidy lot, the new daughter cells start re-forming their internal structures even while they’re still connected along the membrane. The mitotic spindle is the first structure to be broken down, its building blocks recycled into the new cells’ support skeletons. Each set of chromosomes comes together, and the nuclei form, fully-equipped with their own membranes and nucleoli.

Finally, the chromosomes begin to unpack, reforming into long strands of DNA in the nucleus.



Sometimes considered as the later part of telophase, this stage sees the division of cytoplasm (the gooey stuff inside cells) between the two daughters. Cytokinesis can actually start as early as during anaphase (most notably for certain plant cells) but always ends shortly after telophase.

In animal cells, the process of cytokinesis constricts their membranes where they meet — like a piece of string tied around a balloon. That string is a band of actin filaments. The goal of this contraction is to progressively pull the membranes into an ‘8’ shape, after which the cells pop free of each other.

Plant cells, which tend to reinforce their membranes with compounds such as cellulose and hemicellulose, don’t employ the same mechanism. Instead, they form a structure called a cell plate down their middle, splitting the two daughter cells with a new wall.

And voilà! Two new cells, identical to their parent, are now ready to mingle and toil for the collective good.


Despite all the checks and balances biology set in place to make sure mitosis goes through smoothly, sometimes it doesn’t. For cells, any errors that take place during mitosis can have significant effects. For us, multicellular organisms that we are, not so much — but it can still affect us.

One of the most abhorred outcomes of bad mitosis is cancer(link). Faulty copies or improper distribution of chromosomes during mitosis can induce genetic errors, which can cause mutations in daughter cells. Some mutations are silent (they don’t have an impact on the sequence’s role) but those that alter amino acid synthesis (called missense mutations) often have an impact on the cell’s workings. Over time, enough such mutations can add up, disrupting the cell’s normal activity, leading to the formation of tumors. Cancer occurs when mutated tumor cells override their natural limits and checks on mitosis, starting to reproduce uncontrollably.

Another way mitosis can go awry are chromosome abnormalities(link). In short, sometimes the chromosome pairs fail to attach to the spindle, and a daughter cell will end up with an extra or a missing chromosome after division (a condition known as aneuploidy). This error can have far-reaching effects on the body. For context, Down’s syndrome is caused by the presence of an extra chromosome in every cell — it arises from aneuploid sperm or eggs, so it’s a meiotic, not a mitotic error. Still, it illustrates what a body-wide difference of a single chromosome can do. Meiotic chromosomal abnormalities generally only affect one or a small number of cells, based on random mutation.

Cell mutations can also lead to mosaicism(link). This describes a condition in which some cells in the body have a mutant version of a gene, while others carry the normal version. In somatic cells (your body’s cells, bar your eggs or sperm) these mutations generally don’t even produce a noticeable effect. But, if the mutant gene is widespread enough, and is missense, it can have a major impact. Two examples of conditions linked to mosaicism are hemophilia, a blood-clotting disorder, and Marfan syndrome, which produces unusually long limbs.

Cell in shell

Novel cell-in-a-shell is a like a body armor for tiny living things

Researchers from the Imperial College London (ICL) have fused living and non-living cells for the first time; the new entities should allow us to cash in on the abilities of living organisms in harsh applications traditionally relegated to machines.

Cell in shell

An impression of a biological cell (brown) inside the artificial cell (green).
Image credits Imperial College London.

The system encapsulates biological cells within an artificial cell-like casing that allows the two to work together. The system should allow researchers to draw on the natural abilities of biological cells while keeping them safe from environmental threats. For example, the cyborg cells could be used as photosynthesis ‘batteries’, as in-vivo drug factories swimming around your bloodstream, or as biological sensors that can operate in harsh environments.

Rise of the cellborgs

The idea of mixing biological and mechanical systems isn’t new. However, previous work focused on taking part of a cell’s systems, such as certain enzymes or chemical processes, and grafting them into artificial casings. The work at ICL stands out by being the first to take an entire cell and put it in a mechanical shell.

A shell it may be, but it’s far from being just a shell: the artificial component also contains enzymes that work together with those inside the cell to produce new compounds. In the proof-of-concept experiment, the artificial shell produced a fluorescent chemical that allowed the researchers to confirm all was working as expected.

“Biological cells can perform extremely complex functions, but can be difficult to control when trying to harness one aspect, says lead researcher Professor Oscar Ces, from the Department of Chemistry at ICL. “Artificial cells can be programmed more easily but we cannot yet build in much complexity.”

“Our new system bridges the gap between these two approaches by fusing whole biological cells with artificial ones, so that the machinery of both works in concert to produce what we need. This is a paradigm shift in thinking about the way we design artificial cells, which will help accelerate research on applications in healthcare and beyond.”

The team called on a field of knowledge known as microfluidics — which details the behavior of fluids through small channels — to put the two together. They used water and oil (which don’t mix) to make droplets of a defined size that contained both the cells and enzymes. Then, they applied a protective coating on the droplets, creating the artificial shell.

These cellborgs (not an official term, sadly) were then placed in a concentrated copper solution, since copper is usually toxic to biological cells. The team was able to detect the fluorescent chemicals in most of them after immersion, meaning the biological cells were safe inside their shells, still alive and functioning. This ability suggests the bio-artificial cells would be useful in the human body, where foreign biological cells have to contend with attacks by the body’s immune system.

The team went on to explain that their system is “controllable and customizable,” and that they can create different sizes of artificial cells. Furthermore, the casings can be applied to a wide range of cellular machinery “such as chloroplasts for performing photosynthesis or engineered microbes that act as sensors.”

Next on the list is improving the cellborgs’ functionality by improving the artificial shell, in order to make it act more like a biological membrane with extra functions. For example, if it could be designed to open and release the chemicals produced within only in response to certain signals, the cells could be used to deliver drugs to specific areas of the body. This would allow for greater drug efficiency with fewer side-effects — particularly useful for diseases such as cancer.

There’s still have a lot of work to do to get there, but the team says they’ve made a few promising steps in the right directions.

The paper “Constructing vesicle-based artificial cells with embedded living cells as organelle-like modules” has been published in the journal Scientific Reports.

Nanomachines destroy cancer by drilling holes into it

Doctors may someday use fighting nanomachines to puncture cancerous cells and destroy them. These devices are powered by light and spin so fast that they burrow their way through cell linings.

Image credits: Robert Pal/Durham University.

Because cancer is such a complex problem, researchers are trying to take it down from different angles — some more creative than others. Working at Durham University, a team led by Dr. Robert Pal developed motorized molecules that can either deliver drugs or drill holes into specific cells by drilling through their membranes. The key is a paddlelike rotor, a series of three rings of carbon atoms which begin rotating 2 million to 3 million times per second when hit by ultraviolet light. At the same time, the sides of the stator feature arms of carbon, nitrogen, and oxygen that stretch out and selectively grip surface of the cell. Without the rotor, the molecules harmlessly attached themselves to the target cells but didn’t do anything else. This approach could also be used for drug delivery.

These nanomachines are so small that you can fit about 50,000 of them in a width of human hair.

Their potential effectiveness was proven in a trial. It took the between one and three minutes to break through the outer membrane of prostate cancer cell, and once they did, the cell was instantly killed.

“We are moving towards realising our ambition to be able to use light-activated nanomachines to target cancer cells such as those in breast tumours and skin melanomas, including those that are resistant to existing chemotherapy.

“Once developed, this approach could provide a potential step change in non-invasive cancer treatment and greatly improve survival rates and patient welfare globally.”

So far, the molecules have only been tested in vitro (lab tests). Next up, researchers want to test them in vivo, on real life creatures. First up: bacteria and fish. So even if everything goes successfully, it will be quite a while before we can talk about human studies.

Journal Reference: Víctor García-López et al — Molecular machines open cell membranesdoi:10.1038/nature23657