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Published12 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Bernd Debusmann Jr & Robin Levinson-KingBBC NewsA Texas judge has heard arguments about whether a commonly used abortion pill should be sold in the US, in a ruling that could curtail access to the drug nationwide. The pill, mifepristone, can be taken at home and is used in more than half of US pregnancy terminations.A lawsuit filed by an anti-abortion group in Texas argues that the drug’s safety was never properly studied. Mifepristone has been approved for use for over 20 years. The case, which will be decided by Judge Matthew Kacsmaryk, an appointee of former President Donald Trump, follows the US Supreme Court’s historic overruling last year of the constitutional right to abortion. After Wednesday’s four-hour hearing, he said he would issue his ruling as soon as possible.The Texas lawsuit, filed by the Alliance for Hippocratic medicine, an anti-abortion organisation, argues there are three reasons why the drug should be be removed from shelves. One, the lawsuit says the US Food and Drug Administration (FDA) erred by approving the pill under a clause intended to fast-track drugs used for life-threatening illnesses.Two, it argues that the FDA approved mifepristone before adequate testing was carried out. Three, it argues that it is illegal to ship the drug under the Comstock Act, an 1873 law that banned the posting of abortion drugs. However, last December the US Department of Justice’s Office of Legal Counsel issued an opinion that the Comstock Act does not prevent the mailing of abortion medication intended for legal use. In court, Judge Kacsmaryk described the FDA’s approval process as accelerated, according to the Washington Post.The FDA spent four years reviewing the drug before it was approved in 2000.President Joe Biden’s administration has responded to the lawsuit, arguing that mifepristone’s approval was well supported by science.The FDA has reported a total of 26 deaths associated with the drug since it was approved in 2000 – a rate of about 0.65 deaths per 100,000 by-pill abortions. For comparison, the death rate associated with habitual aspirin use is about 15.3 deaths per 100,000 aspirin users.If Judge Kacsmaryk rules that the FDA erred in its approval, sales of the drug – one of only two pills used to induce an abortion – could be halted.Such an unprecedented ruling would essentially upend the entire foundation of America’s independent drug regulatory system, says I. Glenn Cohen, a legal professor at Harvard University. Image source, Getty ImagesThat could affect not only access to the drug for millions of women, but it could cause a chilling effect on drug companies developing new drugs, Prof Cohen said.He said it was possible the case could go all the way to the Supreme Court. If the drug was removed from shelves, women would still be able to use the other approved abortion drug, misoprostol. Misoprostol can be used alone and is often the only option in countries where mifepristone is banned for abortions. Some US clinics and providers also only offer misoprostol. The treatment, however, is slightly less effective than a two-drug regimen that also includes mifepristone.Citing death threats and harassing phone calls, Judge Kacsmaryk had urged attorneys not to publicise the date of Wednesday’s hearing.Some media outlets criticised the rare request, citing transparency concerns, and sent a letter to the court. A small amount of protesters, who are against the lawsuit, gathered outside the federal court in Amarillo.Man sues women for helping ex-wife get abortion ‘Dropbox’ babies – the surrendered infants in USThousands gather for first post-Roe March for LifeJulie Marie Blake, senior counsel for the Alliance Defending Freedom, a conservative group that backs the lawsuit, told the BBC’s US partner CBS that the organisation is “confident that when any court looks at the law and looks at the science, it will realise that the FDA has completely failed its responsibility to protect women and girls”. Meanwhile, twelve Democratic-led states, including Washington, Arizona, Colorado, Delaware and Connecticut, have filed a separate lawsuit against the FDA seeking to make access to mifepristone easier. That legal action alleges that the FDA’s current regulations concerning the drug are “burdensome, harmful and unnecessary”.More on this story12 US states sue to expand access to abortion pill24 FebruaryUS Supreme Court fails to find abortion news leaker19 JanuaryUS pharmacies can now sell abortion pills4 January

The sex hormone estrogen has a negative impact on heartbeat regulation, according to an experimental study from Linköping University, Sweden, published in Science Advances. Estrogen impact seems to interact with hereditary changes causing a heart disease disturbing the heart’s rhythm, while other endogenous substances may have a protecting effect.
In a lifetime, the heart beats around 2.5 billion times. Each heartbeat is triggered by an electrical impulse that causes the heart muscle to contract in a very well-coordinated movement. The heart’s electrical activity is regulated by small pores, ion channels, that go through the cell’s membranes and regulate the flow of electrically charged ions in and out of the cell. Some ion channels act as an accelerator and others as a brake. Together, they regulate every heartbeat throughout life.
Diseases causing an abnormal heart rhythm may, in some cases, be deadly. Long QT syndrome, LQTS, is one such disease. In LQTS patients, the heart takes longer than normal to finish every heartbeat. This syndrome is most often due to a congenital hereditary change, or mutation, affecting one of the heart’s ion channels.
“We’re trying to understand which substances in the body impact the function of the ion channels. If we could figure out how this regulation works, maybe we can understand why some individuals are more protected and others are hit harder,” says Sara Liin, associate professor in the Department of Biomedical and Clinical Sciences at Linköping University, LiU.
In this study, the researchers have taken an interest in possible effects of the sex hormone estrogen. They came up with this idea when asked by heart specialists why women are not only more often affected than men, but also more severely affected, by certain hereditary diseases causing an abnormal heart rhythm, also known as arrhythmia. This in light of the fact that women are generally seen as having better protection against cardiovascular diseases. Could it have anything to do with women having more estrogen than men?
In their study, the researchers studied the type of ion channel most often mutated in LQTS, which is called Kv7.1/KCNE1. Reduced function of this ion channel is a risk factor increasing the risk of arrhythmia. To be able to understand estrogen impact on this specific ion channel, the researchers conducted experiments where they inserted the human variant of the ion channel into frogs’ eggs, which do not have this ion channel. The researchers added the most active form of the sex hormone estrogen, estradiol, and measured the ion channel function. It turned out that ion channel function was hampered by estrogen, which the researchers interpret as an indication that estrogen may increase the risk of certain types of arrhythmia. Other sex hormones had no effect.
The researchers also found out exactly which parts of the channel were impacted by estrogen. They further examined ion channel mutations found in families with hereditary arrhythmia syndromes. Some mutations led to high estrogen sensitivity, while others led to the ion channel completely losing estrogen sensitivity.
“We show that some hereditary mutations that reduce ion channel function seem to contribute to high estrogen sensitivity, so there could be two risk factors that interact especially in women carriers of these mutations. We believe that our study gives good reason to look closer at this in patients,” says Sara Liin.
The researchers point out that it is important to remember the many positive effects of estrogen, and that in women with a hereditary increased risk of LQTS, estrogen could possibly be a risk factor. LQTS is relatively rare, affecting around 1 in 2,500 people.
The LiU researchers recently published a study in The Lancet eBioMedicine where they conducted a similar study into a group of endogenous substances known as endocannabinoids. This study showed that endocannabinoids instead seemed to function as protective factors in LQTS. According to the researchers, the findings indicate that these factors may be important to study in humans, as this may lead to ways of increasing endocannabinoid levels to counteract arrhythmia.
The study was financed with support from, among others, the European Research Council, ERC, via the Horizon 2020 research programme.

Consuming a diet rich in vitamin A or its analogs may help prevent children and young adults with acute lymphoblastic leukemia (ALL) reduce their risk of developing painful pancreas inflammation during chemotherapy treatment.
Details about this potential dietary solution to prevent a potentially life-threatening adverse event were published March 15, 2023, in Science Translational Medicine. The research team was led by Sohail Husain, MD, chief of Pediatric Gastroenterology, Hepatology, and Nutrition at Stanford University and Anil Goud Jegga, DVM, MRes, a computational biologist at Cincinnati Children’s Hospital Medical Center.
For people with ALL, treatment with the enzyme asparaginase helps starve cancer cells by reducing the amount of asparagine circulating in the blood, which the cancer cells need but cannot make themselves. The medication, often used in combination with other chemotherapies, is given via injection into a vein, muscle, or under the skin.
However, an estimated 2% to 10% of asparaginase users develop inflammation of the pancreas in reaction to asparaginase treatment. For a third of these people, the symptoms can be severe.
Jegga and colleagues developed predictive analytics using over 100 million data points encompassing gene expression data, small-molecule data, and electronic health records to understand more of the mechanisms driving asparaginase-associated pancreatitis (AAP) and identify potential interventions to prevent or mitigate AAP.
First, they analyzed massive amounts of gene expression data to reveal that gene activity associated with asparaginase or pancreatitis might be reversed by retinoids (vitamin A and its analogs). The team found more supporting evidence by “mining” millions of of electronic health records from the TriNetX database and the U.S. Federal Drug Administration Adverse Events Reporting System.
This number crunching and predictive analytics work included use of the AERSMine software developed at Cincinnati Children’s by Mayur Sarangdhar, PhD, MRes, and colleagues. The research team also studied data from mice experiments and compared plasma samples from people with ALL who developed pancreatitis and those who did not.
Ultimately, the team established two sets of human “real-world” experiences. They found that only 1.4% of patients treated with asparaginase developed pancreatitis when they were also taking vitamin A in contrast to 3.4% of patients who did not. Concomitant use of vitamin A correlated with a 60% reduction in the risk of AAP. Lower amounts of dietary vitamin A correlated with increased risk and severity of AAP.
“This study demonstrates the potential of mining ‘real-world’ data to identify therapy modifiers for improving patient outcomes. In cases where a primary drug induces toxicity but is critical to therapy, such as asparaginase, therapy modifiers, such as vitamin A and its analogs, may be of immediate relevance to patients on asparaginase and ‘at-risk’ for AAP,” says Sarangdhar, a co-first author of the study.
Says Jegga: “Our study highlights the power of heterogeneous data integration and analysis in translational research. By leveraging existing ‘omics and patient-centric data and a systems approach, we were able to identify new insights into the development of AAP and potential interventions to prevent or mitigate this side effect.”
Next steps
In some ways, learnings from this study could be applied immediately to patient care. However, more clinical research is needed to establish how much vitamin A would be needed to protect ALL patients from pancreatitis; and whether a protective level can be achieved by diet or via supplements. In fact, target vitamin levels may need to vary according to individual differences in metabolism.

Published14 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Family photoAn ambulance worker who caught Covid from a patient died as the result of an industrial disease, a coroner has concluded.Alan Haigh, 59, from Cwmduad, Carmarthenshire, died in Glangwili Hospital on 9 February 2021.He was involved in the transport of a patient to the red Covid ward at Prince Philip Hospital on the 28 November.Coroner Paul Bennett said the greatest risk to him was “his employment.”The acting senior coroner for Carmarthenshire and Pembrokeshire said he thought there was sufficient evidence that Mr Haigh had “two incidents of exposure” to Covid during the possible incubation period for the disease.Tributes to ‘full of life’ Welsh ambulance workerNurses who died probably caught Covid at workCovid in Wales: What do the stats tell us? Mr Haigh was working on the frontline as an emergency medical technician when he caught Covid. He began displaying symptoms on the 30th November.The inquest heard that Mr Haigh told a colleague he thought he had caught the virus from a patient.He was admitted to hospital on 7 December 2020 and died two months later.Image source, Family photoHis wife Sian Haigh said her husband always took extra measures to protect himself and his family during the pandemic as she had asthma and her mother was vulnerable.He was the third ambulance worker to die from Covid-19 in Wales, following call handler Paul Teesdale and paramedic Gerallt Davies.Mr Haigh joined the ambulance service in 1998 and had become a grandfather just four months before his death.He was described by colleagues as a “full-of-life character who loved to chat”. His son Colin Haigh, 32, read a tribute on behalf of the family, thanking all the staff who cared for his father.”The sight of hundreds of NHS staff, ambulance personnel and friends that lined the streets in a show of support and kinship for his funeral will live long in our memories,” he said.”We were completely overwhelmed and immensely touched.”Speaking personally, dad was always happy, loving and caring. To this day we all miss him and we are all proud of him.”Mr Bennett said he hoped the inquest “would bring some closure” and that Mr Haigh’s death “was not easy to deal with”.More on this storyNHS worker caught Covid from patient, inquest hears1 day agoNurses who died probably caught Covid at work13 JanuaryCovid-19 in the UK23 December 2022Covid in Wales: What do the stats tell us?5 days agoTributes to ‘full of life’ Welsh ambulance worker9 February 2021

Researchers at ETH Zurich, Empa and EPFL are developing a 3D-​printed insole with integrated sensors that allows the pressure of the sole to be measured in the shoe and thus during any activity. This helps athletes or patients to determine performance and therapy progress.
In elite sports, fractions of a second sometimes make the difference between victory and defeat. To optimize their performance, athletes use custom-​made insoles. But people with musculoskeletal pain also turn to insoles to combat their discomfort.
Before specialists can accurately fit such insoles, they must first create a pressure profile of the feet. To this end, athletes or patients have to walk barefoot over pressure-​sensitive mats, where they leave their individual footprints. Based on this pressure profile, orthopaedists then create customised insoles by hand. The problem with this approach is that optimisations and adjustments take time. Another disadvantage is that the pressure-​sensitive mats allow measurements only in a confined space, but not during workouts or outdoor activities.
Now an invention by a research team from ETH Zurich, Empa and EPFL could greatly improve things. The researchers used 3D printing to produce a customised insole with integrated pressure sensors that can measure the pressure on the sole of the foot directly in the shoe during various activities.
“You can tell from the pressure patterns detected whether someone is walking, running, climbing stairs, or even carrying a heavy load on their back — in which case the pressure shifts more to the heel,” explains co-​project leader Gilberto Siqueira, Senior Assistant at Empa and at ETH Complex Materials Laboratory. This makes tedious mat tests a thing of the past.
One device, multiple inks
These insoles aren’t just easy to use, they’re also easy to make. They are produced in just one step — including the integrated sensors and conductors — using a single 3D printer, called an extruder.

For printing, the researchers use various inks developed specifically for this application. As the basis for the insole, the materials scientists use a mixture of silicone and cellulose nanoparticles.
Next, they print the conductors on this first layer using a conductive ink containing silver. They then print the sensors on the conductors in individual places using ink that contains carbon black. The sensors aren’t distributed at random: they are placed exactly where the foot sole pressure is greatest. To protect the sensors and conductors, the researchers coat them with another layer of silicone.
An initial difficulty was to achieve good adhesion between the different material layers. The researchers resolved this by treating the surface of the silicone layers with hot plasma.
As sensors for measuring normal and shear forces, they use piezo components, which convert mechanical pressure into electrical signals. In addition, the researchers have built an interface into the sole for reading out the generated data.
Running data soon to be read out wirelessly
Tests showed the researchers that the additively manufactured insole works well. “So with data analysis, we can actually identify different activities based on which sensors responded and how strong that response was,” Siqueira says.

At the moment, Siqueira and his colleagues still need a cable connection to read out the data; to this end, they have installed a contact on the side of the insole. One of the next development steps, he says, will be to create a wireless connection. “However, reading out the data hasn’t been the main focus of our work so far.”
In the future, 3D-​printed insoles with integrated sensors could be used by athletes or in physiotherapy, for example to measure training or therapy progress. Based on such measurement data, training plans can then be adjusted and permanent shoe insoles with different hard and soft zones can be produced using 3D printing.
Although Siqueira believes there is strong market potential for their product, especially in elite sports, his team hasn’t yet taken any steps towards commercialisation.
Researchers from Empa, ETH Zurich and EPFL were involved in the development of the insole. EPFL researcher Danick Briand coordinated the project, and his group supplied the sensors, while the ETH and Empa researchers developed the inks and the printing platform. Also involved in the project were the Lausanne University Hospital (CHUV) and orthopaedics company Numo.

Learning, remembering something, and recalling memories is supported by multiple separate groups of neurons connected inside and across key regions in the brain. If these neural assemblies fail to sync together at the right time, the memories are lost, a new study led by the universities of Bristol and Heidelberg has found.
How do you keep track of what to do next? What happens in the brain when your mind goes blank? Short-term memory relies on two key brain regions: the hippocampus and the prefrontal cortex. The researchers set out to establish how these brain regions interact with one another as memories are formed, maintained and recalled at the level of specific groups of neurons. The study, published in Currently Biology, also wanted to understand why memory sometimes fails.
“Neural assemblies” — groups of neurons that join forces to process information — were first proposed over 70 years ago, but have proved difficult to pinpoint.
Using brain recordings in rats, the research team has shown that memory encoding, storage and recall is supported by dynamic interactions incorporating multiple neural assemblies formed within and between the hippocampus and prefrontal cortex. When the coordination of these assemblies fails, the animals made mistakes.
Dr Michał Kucewicz, Assistant Professor of Neurology at Gdansk University of Technology, formerly a PhD student at the University of Bristol, and lead author, said: “Our results make potential therapeutic interventions for memory restoration more challenging to target in space and time. On the other hand, our findings have identified critical processes that determine a success or failure in remembering. These present viable targets for therapeutic interventions on the level of neural assembly interactions.”
Matt Jones, Professor of Neuroscience in the School of Physiology, Pharmacology and Neuroscience and Bristol Neuroscience and senior author of the paper, added: “Our findings add to evidence that the neural substrates of memory are more distributed in anatomical space and dynamic across time than previously thought based on the neuropsychological models.”
The next steps for the research would be to modulate neural assembly interactions, either using drugs or via brain stimulation, which Dr Kucewicz is currently doing in human patients, to test whether disrupting or augmenting them would impair or enhance remembering. The research team presumes the same mechanisms would work in human patients to restore memory functions impaired in a particular brain disorder.

It may be better to let a mild fever run its course instead of automatically reaching for medication, new University of Alberta research suggests.
Researchers found that untreated moderate fever helped fish clear their bodies of infection rapidly, controlled inflammation and repaired damaged tissue. “We let nature do what nature does, and in this case it was very much a positive thing,” says immunologist Daniel Barreda, lead author on the study and a joint professor in the Faculty of Agricultural, Life & Environmental Sciences and the Faculty of Science.
Moderate fever is self-resolving, meaning that the body can both induce it and shut it down naturally without medication, Barreda explains. The health advantages of natural fever to humans still have to be confirmed through research, but the researchers say because the mechanisms driving and sustaining fever are shared among animals, it is reasonable to expect similar benefits are going to happen in humans.
That suggests we should resist reaching for over-the-counter fever medications, also known as non-steroidal anti-inflammatory drugs, at the first signs of a mild temperature, he says. “They take away the discomfort felt with fever, but you’re also likely giving away some of the benefits of this natural response.”
The study helps shed light on the mechanisms that contribute to the benefits of moderate fever, which Barreda notes has been evolutionarily conserved across the animal kingdom for 550 million years. “Every animal examined has this biological response to infection.”
For the study, fish were given a bacterial infection and their behaviour was then tracked and evaluated using machine learning. Outward symptoms were similar to those seen in humans with fever, including immobility, fatigue and malaise. These were then matched to important immune mechanisms inside the animals.
The research showed that natural fever offers an integrative response that not only activates defences against infection, but also helps control it.The researchers found that fever helped to clear the fish of infection in about seven days — half the time it took for those animals not allowed to exert fever. Fever also helped to shut down inflammation and repair injured tissue.
“Our goal is to determine how to best take advantage of our medical advances while continuing to harness the benefits from natural mechanisms of immunity,” says Barreda.

New research from the University of Missouri School of Medicine has established a link between western diets high in fat and sugar and the development of non-alcoholic fatty liver disease, the leading cause of chronic liver disease.
The research, based in the Roy Blunt NextGen Precision Health Building at MU, has identified the western diet-induced microbial and metabolic contributors to liver disease, advancing our understanding of the gut-liver axis, and in turn the development of dietary and microbial interventions for this global health threat.
“We’re just beginning to understand how food and gut microbiota interact to produce metabolites that contribute to the development of liver disease,” said co-principal investigator, Guangfu Li, PhD, DVM, associate professor in the department of surgery and Department of Molecular Microbiology and Immunology. “However, the specific bacteria and metabolites, as well as the underlying mechanisms were not well understood until now. This research is unlocking the how and why.”
The gut and liver have a close anatomical and functional connection via the portal vein. Unhealthy diets change the gut microbiota, resulting in the production of pathogenic factors that impact the liver. By feeding mice foods high in fat and sugar, the research team discovered that the mice developed a gut bacteria called Blautia producta and a lipid that caused liver inflammation and fibrosis. That, in turn, caused the mice to develop non-alcoholic steatohepatitis or fatty liver disease, with similar features to the human disease.
“Fatty liver disease is a global health epidemic,” said Kevin Staveley-O’Carroll, MD, PhD, professor in the department of surgery, one of the lead researchers. “Not only is it becoming the leading cause of liver cancer and cirrhosis, but many patients I see with other cancers have fatty liver disease and don’t even know it. Often, this makes it impossible for them to undergo potentially curative surgery for their other cancers.”
As part of this study, the researchers tested treating the mice with an antibiotic cocktail administered via drinking water. They found that the antibiotic treatment reduced liver inflammation and lipid accumulation, resulting in a reduction in fatty liver disease. These results suggest that antibiotic-induced changes in the gut microbiota can suppress inflammatory responses and liver fibrosis.
Li, Staveley-O’Carroll and fellow co-principal investigator R. Scott Rector, PhD, Director of NextGen Precision Health Building and Interim Senior Associate Dean for Research — are part of NextGen Precision Health, an initiative to expand collaboration in personalized health care and the translation of interdisciplinary research for the benefit of society. The team recently received a $1.2 million grant from the National Institutes of Health to fund this ongoing research into the link between gut bacteria and liver disease.

Researchers from Tokyo Medical and Dental University (TMDU) shed new light on the characteristics of the niche in which neural stem cells reside in the developing brain.
Tokyo, Japan — When it comes to cell types, stem cells have unlimited potential — literally. These self-renewing cells, which are capable of giving rise to any cell type in the body, reside in specialized microenvironments known as niches. Now, researchers in Japan have shed new insight into the dynamics of the neural stem cell niche, the home of stem cells in the brain.
In a new study published in Inflammation and Regeneration, researchers from Tokyo Medical and Dental University (TMDU) investigated the effects of hypoxic (low oxygen) conditions on the neural stem cell niche during development.
Neural stem and progenitor cells (NPSCs) give rise to the cells of the brain and nervous system. NSPCs are known to reside in a hypoxic niche, meaning that oxygen levels in the niche are lower than those of the surrounding tissues. However, the composition of this niche, and how NSPCs maintain themselves within it, is not entirely clear. The TMDU-led research team set out to investigate the effects of low oxygen conditions within the neural stem cell niche using a cell culture model of NSPCs isolated from the forebrains of embryonic mice. They cultured these cells into neurospheres, or free-floating stem cell clusters, under low-oxygen and normal-oxygen conditions.
“The results were striking, with significantly increased neurosphere formation observed under hypoxic conditions compared with normoxic conditions,” says co-lead author of the study Taichi Kashiwagi. “This led us to explore what factors play a role in the maintenance and proliferation of NSPCs under hypoxic conditions.”
The researchers evaluated a protein called vascular endothelial growth factor-A (VEGF-A) as a potential candidate. When the research team added VEGF-A to the NSPC cultures, neurosphere formation was significantly increased. Conversely, blocking VEGF-A with a drug inhibitor diminished the increase in neurosphere formation under low oxygen conditions. Additionally, VEGF-A expression was found to be upregulated in NSPCs under low oxygen conditions.
“We found that NSPCs treated with VEGF-A showed lower rates of cell death and increased cell proliferation,” says senior author Tetsuya Taga. “VEGF-A is a factor that appears to contribute to NSPC maintenance under low oxygen conditions.”
These findings indicate that NSPCs help to maintain their own population through the release of VEGF-A under hypoxic conditions. While other factors may also contribute to NSPC maintenance, these results shed new light on the composition of the neural stem cell niche during development, and may serve as a foundation for further studies of self-organization of the hypoxic niche.

Proteins are the heavy-lifters of biochemistry. These beefy molecules act as building blocks, receptors, processors, couriers and catalysts. “Proteins are the molecular machines that power all life on Earth,” explained Mark Sherwin, a physics professor at UC Santa Barbara. Naturally, scientists have devoted a lot of research to understanding and manipulating proteins.
A team led by researchers at UC Santa Barbara, including Sherwin, has made strides in addressing one of the grand challenges of modern science: recording proteins in motion in a lifelike environment. The authors discuss their technique in Angewandte Chemie, a journal of the German Chemical Society. The approach could revolutionize our understanding of how proteins do their jobs and guide the design of proteins for specific purposes.
A daunting challenge
Understanding a protein’s function requires more than merely a list of its parts. For these molecules, form begets function. Scientists have made enormous progress in the last 20 years deciphering proteins’ shapes based on the amino acid building blocks that form them.
However, even seeing a machine’s shape often isn’t enough to understand how it works. “Imagine you are an alien, and you see a picture of a sewing machine,” Sherwin said. “You would have a hard time figuring out what it does. But if you saw a movie, you would have a much better idea.”
Unfortunately, this is a tall order for proteins. Although they are relatively large molecules, proteins are still only a few nanometers in size, 100 times smaller than we can resolve even with the most powerful optical microscopes. And they exist in wet, squishy environments not conducive to cinematography.

“One of the biggest challenges in biology in general is to see proteins in action,” explained co-lead author Shiny Maity, a chemistry doctoral student. It is much easier for scientists to look at the structure of proteins when they’re frozen. To see them move requires a technique like stop-motion animation: start the action, freeze the protein, capture an image, repeat. This is often prohibitively difficult for both fast and slow movement. On top of that, flash freezing the protein can affect its structure.
“The goal that we have is to take out the freezing aspect completely and look at the motion of the protein in as close to a lifelike environment as we can get,” said co-lead author Brad Price, a physics graduate student.
An intricate technique
This paper demonstrates a new method to track the movement of proteins in a lifelike environment after their motion has been triggered by an external event (in this case, a visible light pulse). The authors call the technique TiGGER, for Time Resolved Gadolinium-Gadolinium Electron paramagnetic Resonance. It is elaborate, requiring quantum phenomena, skilled chemistry, specialty equipment and bioengineering.
TiGGER involves tagging two spots on the protein and tracking the distance between these labels as the protein unfolds and refolds. The star of the show is a charged gadolinium atom, or ion. Its electrons line up in such a way that the ion behaves like a little magnet. If you place it in a strong magnetic field, it will align with or against the external field and begin to wobble.

Scientists stick the gadolinium in a molecular cage to stabilize it and add some chemical scaffolding to link it with the protein. But those bits only link to one type of amino acid, cysteine. So the team had to change the amino acids they wanted to tag into cysteines without affecting the protein’s overall function. It was a task made even trickier by a cysteine in the center of the protein that is critical to its function.
“The spin label is chosen very strategically,” Maity said. “It is big enough not to enter the core of the protein, where the functional cysteine is located. But it’s also not too big that it disrupts the protein’s natural shape.”
The wobbling, or “precession,” of the gadolinium ion is influenced by the proximity of the other tag, which has its own wobbling gadolinium ion generating its own little magnetic field. This precession changes based on how close the two tags are to each other. Measure this wobble, and you can derive the distance.
This is precisely what the authors did using a laser with light at energies slightly higher than those in a microwave oven. When the frequency of these sub-Terahertz waves and the ion’s precession match up, the waves are absorbed. The scientists then measured this absorption to detect small changes in the gadolinium’s precession. If the amount of absorption changes with time, that means the tags are moving.
Add some more mathematics, and the authors could even tell you how far apart the tags are from one another. “We know that we can get distance as a function of time, but it will take more development,” Price said.
An illuminating protein
The authors selected a popular and versatile protein to develop TiGGER. Their model belongs to the light, oxygen or voltage (LOV) sensitive family of proteins, specifically a light-activated protein called AsLOV2. “LOV proteins control processes ranging from circadian rhythms in bacteria, plants and fungi to phototropism in plants and microorganisms,” said co-author Max Wilson, an assistant professor in the Department of Molecular, Cellular and Developmental Biology. “In summary, they are intimately connected to light sensing.”
This property makes AsLOV2 popular with scientists and engineers, and simple to manipulate. “It’s interesting and a perfect test case,” Price said, “a best-of-both-worlds situation.”
LOV proteins enable scientists to use light as a “remote control” for a whole host of molecular processes in cells. “We use it to control stem cell differentiation, antibody binding, stiffening and relaxation of extracellular matrix proteins, and activation of cellular signaling pathways,” Wilson said.
Assistant professor Arnab Mukherjee, of the chemical engineering department, uses LOV proteins to track biochemical processes in living cells using fluorescence, much like a highlighter under a black light. “Unlike conventional fluorescent proteins, LOV proteins operate by a distinct mechanism that makes their ‘glow’ visible even in oxygen-free conditions,” he explained. This offers a tool to study microbes living in anaerobic environments, like the human gut.
But it’s tricky to engineer these proteins to do what researchers want. This is where TiGGER comes in handy. If scientists like Wilson and Mukherjee can see the proteins in motion, they could be more deliberate in their design processes.
An eye toward the future
Senior authors Sherwin and Songi Han, a professor of chemistry, first began their quest to film proteins in 2006, however it’s still early days for TiGGER. Right now, the technique can produce a one-dimensional trajectory of a protein’s movement between two points. But its true power comes from repeating the technique at several different sites. This enables scientists to piece together the motion of the protein as a whole. They can then map this movement onto a model of the protein to create a movie in a similar manner to the CGI animation that brings our favorite cartoon characters to life.
The authors are focused on optimizing the technique before they invest the time applying it to other sites on AsLOV2. They are working to increase the signal-to-noise ratio and bump up the sampling speed of their instruments. The team also hopes to slow down the random motion of the proteins as they’re suspended in solution, which should enable them to capture sharper footage than they can now.
In the meantime, Price and Maity are using TiGGER to answer some basic questions about AsLOV2. For instance, why does the protein unfold over 1,000 times faster than it refolds? And how do mutations that are known to affect refolding affect unfolding? They’re also investigating how hotter conditions affect the protein’s function. The results could shed light on how oats — the source of AsLOV2 — will respond to climate change.
Eventually, TiGGER can be translated to all sorts of other proteins, as long as the scientists can modify the sites of interest into cysteine amino acids without affecting the protein’s function. “Biophysicists have been striving to ‘film’ proteins in motion to gain an in-depth understanding of their biological functions,” Maity said. “TiGGER has the potential to make this dream come true.”