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SharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesThe UK government was not properly prepared for a pandemic like Covid-19, a new report has found. The report by the National Audit Office (NAO) said the government lacked detailed plans on shielding, job support schemes and school disruption.The spending watchdog added that lessons needed to be learned.In response, the government said the unprecedented pandemic had challenged health systems around the world – not just the UK.The NAO said preparations for a flu pandemic or highly infectious diseases like Ebola were prioritised over diseases with similar characteristics to Covid. The watchdog said the UK government did not have specific plans to tackle a disease like Covid-19, which has a lower mortality rate than Ebola but has the ability to spread in communities with asymptomatic infected people. The report suggests the government had some mitigations in place for a pandemic, like a stockpile of personal protective equipment, but it lacked preparation for “wide-ranging impacts” coronavirus and other pandemic-inducing viruses can have on society and the economy. The government announced the furlough scheme, which originally covered 80% of wages for staff who were unable to work due to the pandemic, on 20 March – three days before the first national lockdown was brought in. And on 21 March the government began sending letters to people identified as vulnerable to Covid, advising them to stay at home and “shield”. However, the NAO report found the government lacked detailed plans for such measures. The report also found that the Cabinet Office allocated 56 of its 94 full-time emergency planning members of staff to prepare for potential disruptions from a no-deal exit from the European Union, “limiting its ability” to plan for other crises.Where are we at with Covid?What’s the plan to manage Covid this winter?When will the UK’s Covid public inquiry happen?The watchdog found that the pandemic “exposed a vulnerability to whole-system emergencies”, suggesting there was “limited oversight and assurance” of the plans in place. The report said the government missed the opportunity to learn from previous large-scale pandemic simulations it carried out as far back as 2007. One simulation, Exercise Cygnus, which ran in 2016, suggested the government should consider “the ability of staff to work from home”.However, at the beginning of the Covid pandemic “many departmental business continuity plans did not include arrangements for extensive home working”, the watchdog said.A government spokesperson said: “We have always said there are lessons to be learned from the pandemic and have committed to a full public inquiry in spring.”We prepare for a range of scenarios and while there were extensive arrangements in place, this is an unprecedented pandemic that has challenged health systems around the world.”Labour’s shadow Cabinet Office minister Fleur Anderson, said the report showed “Conservative ministers failed to prepare and they failed the public”.BANISH YOUR BRAIN FOG: Quick tips to boost energy this winter!HOW ‘BRITISH’ IS BRITISH TV?: The role of public service broadcasters with the influx of US programmes

SharecloseShare pageCopy linkAbout sharingImage source, Benjamin Vedrenne-CloquetPatients with a rare genetic condition that causes progressive muscle weakness are to benefit from a new treatment available on the NHS in England.Risdiplam, an oral medicine taken once a day, has been shown in trials to improve muscle movement and control in patients with Spinal Muscular Atrophy (SMA).It is the third approved SMA treatment in the past three years. Unlike others, it does not involve an injection and can be taken at home.The inherited disease leads to the loss of nerve cells involved in walking, crawling, sitting, breathing and swallowing. Risdiplam boosts the level of a key protein lacking in patients with SMA. This is expected to increase survival of nerve cells that control movement to manage the symptoms of the disease and slow down its progression.More than 200 patients in England have already had risdiplam via an early access scheme and NHS England says several hundred more will now benefit who have a diagnosis of SMA types 1,2 or 3.Image source, Benjamin Vedrenne-CloquetMelvil Vedrenne-Cloquet, who is nine and from south London, has been on risdiplam for nearly four years.His father, Benjamin Vedrenne-Cloquet, is French and enrolled him on a clinical trial in Paris. Benjamin told the BBC: “It’s great to see Melvil improving a little bit every day. He has more stamina and is able to handle the stairs better.”We felt very privileged to have been able to access this drug before other patients in the UK and we are delighted it will be more widely available now.”Of the three main types of SMA, type 1 is the most serious. Without treatment, children mostly don’t survive beyond the age of two. Melvil has type 3 where the decline in function is far more gradual. Difficulties with standing and walking may develop, but life expectancy is not usually affected.Melvil recorded a video when he started a new school to explain his condition to other pupils. In it he said: “SMA makes my legs and belly muscles weak and work very differently to yours. I cannot run or jump. I can walk slowly. One metre for me, is the same as five metres for you.” The two other treatments for SMA have to be given in hospital, by injection. They include a one-off gene therapy Zolgensma, which has a list price of nearly £2m, making it the world’s most expensive medicine.’Gene therapy is a game changer for our son’The second treatment, Spinraza (nusinersen) is given by spinal injection four times per year. It costs £450,000 in the first year, though, as with Zolgensma and risdiplam (Evrysdi), the NHS has negotiated a confidential discount. Risdiplam costs £7,900 per bottle and may last patients just a couple of weeks as dosage depends on weight. Chris Towler, who is 25, has type 3 SMA and is one of many who could potentially benefit from risdiplam. In the past two years he has lost the ability to walk while waiting for Spinraza. Chris, who has a masters in sports management and is a coach, says he has a positive attitude but is not optimistic that he will get either treatment quickly. Nonetheless he says it would make a big difference. “Just to have the certainty that it is not going to get any worse would be huge. I may not get back my ability to walk, that’s fine. I’m still happy in the skin that I live in,” he said.Dr Elizabeth Wraige, consultant paediatric neurologist at Evelina Hospital in London, said: “We now have options for patients with all three types of spinal muscular atrophy. If someone’s not able to receive one type of treatment, maybe they will be able to take one of the others. I think it makes a huge change. It really alters the outlook for people with SMA and gives them hope for the future.”NHS England chief executive Amanda Pritchard said: “In the last three years the NHS has revolutionised care for people with SMA, by securing access to a trio of innovative treatments- Spinraza, Zolgensma and now risdiplam- where three years ago clinicians had no effective medicines at all.”Spinal Muscular Atrophy is a cruel disease and the leading genetic cause of death among babies and young children, which is why NHS England has been determined to make these treatment available to people as soon as possible to help transform the lives of patients and their families. SMA UK said: “We’re absolutely delighted. Risdiplam offers so much more flexibility in people’s lives. We will continue to advocate for its provision across all the UK.”The charity is campaigning for newborn screening for SMA. Spinal Muscular Atrophy UKThe BBC is not responsible for the content of external sites.

In the human brain, the hormone insulin also acts on the most important neurotransmitter for the reward system, dopamine. This was shown by researchers from the German Center for Diabetes Research (DZD) in Tübingen. Insulin lowers the dopamine level in a specific region of the brain (striatum *) that regulates reward processes and cognitive functions, among other things. This interaction can be an important driver of the brain’s regulation of glucose metabolism and eating behavior. The study has now been published in the Journal of Clinical Endocrinology & Metabolism.
Worldwide, more and more people are developing obesity and type 2 diabetes. Studies show that the brain plays an important role in causing these diseases. Dopamine is the most important neurotransmitter for the reward system. The hormone insulin is released after eating and regulates the metabolism in the human body (homeostatic system). It is not yet known how these two systems interact. However, changes in these systems have been linked to obesity and diabetes. In the current study, researchers from the Institute of Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Zentrum München at the University of Tübingen, a partner of the DZD, and Tübingen University Hospital (Innere IV, Director: Prof. Andreas Birkenfeld) examined how the two systems interact specifically in the reward center of the brain, the striatum.
“Our eating behavior is regulated by the interaction between the reward system and homeostatic systems. Studies indicate that insulin also acts in dopamine-driven reward centers in the brain. It has also been shown that obesity leads to changes in the signaling of the brain that have a negative effect on the glucose metabolism in the whole body,” said first author Stephanie Kullmann. “We now wanted to decipher the interaction between the two systems in humans and find out how insulin regulates the dopamine system.”
For this purpose, ten healthy, normal-weight men received insulin or a placebo via a nasal spray (randomized, placebo-controlled, blinded crossover study). When insulin is absorbed via the nose, it reaches the brain directly. To study the interaction between insulin and dopamine, the researchers used a unique measurement technique: they combined magnetic resonance imaging to assess functional brain activity and positron emission tomography to assess dopamine levels.
Analysis of the study showed that the intranasal administration of insulin lowered dopamine levels and led to changes in the brain’s network structure. “The study provides direct evidence of how and where in the brain signals triggered after eating — such as insulin release and the reward system — interact,” said Professor Martin Heni, last author of the study, summarizing the results. “We were able to show that insulin is able to decrease dopamine levels in the striatum in normal-weight individuals. The insulin-dependent change in dopamine levels was also associated with functional connectivity changes in whoe-brain networks. Changes in this system may be an important driver of obesity and related diseases.”
In further studies, the researchers want to investigate changes in the interaction of dopamine and insulin in obese or diabetic participants. These people often suffer from insulin resistance in the brain. The researchers therefore assume that this resistance prevents the normal insulin-induced regulation of dopamine levels in the reward center. In further steps, they want to restore the normal action of insulin in the brain by behavioral and/or pharmaceutical interventions.
* Striatum The striatum belongs to the human cerebrum and forms part of the basal ganglia. It is a central connection point for various neural pathways as well as control circuits and is involved in the interaction of motivation, reward, emotion, movement behavior and numerous cognitive functions.
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Materials provided by Deutsches Zentrum fuer Diabetesforschung DZD. Note: Content may be edited for style and length.

Now that the Human Genome Project has officially wrapped, an international team of researchers will map the entire collection of proteins in the human body.
Plans and goals for the Human Proteoform Project were outlined in a paper published last week (Nov. 12) in the journal Science Advances. The large undertaking will characterize known proteoforms (specific protein molecules) as well as aim to systematically discover and analyze new ones in human tissues, cells and fluids.
“We are all built of proteins, and most drugs target proteins,” said Northwestern University’s Neil Kelleher, a proteomics pioneer and corresponding author of the paper. “But understanding proteins is an open frontier. Like other seminal moments in science and technology, this project will serve as a major achievement that can help us more fully understand proteins’ role in all types of disease, aging and new therapeutics.”
Kelleher is the Walter and Mary Glass Professor of Molecular Biosciences and professor of chemistry in Northwestern’s Weinberg College of Arts and Sciencesand a professor of medicine in Northwestern University Feinberg School of Medicine.He also is director of the Chemistry of Life Processes Institute(CLP) and faculty director of Northwestern Proteomics, a center of excellence within CLP that develops novel platforms for drug discovery and diagnostics. Kelleher co-authored the paper with the Consortium for Top-Down Proteomics.
The human body comprises at least 20,000 individual genes — and from each gene, proteins are processed into various forms (or proteoforms). So, for the 20,300 genes, there are millions of unique proteoforms created due to genetic variation, modification or alternative splicing.
“There is a proteoform family for every human gene,” Kelleher said. “And proteoforms have a life of their own. They can be activated or repressed after they are produced, and their diversity varies widely in our different cell types in unknown ways. Understanding the exact proteins we are made of is complex and challenging and will require a major global effort.”
The Human Proteoform Project’s ultimate goal is to establish a definitive and comprehensive Human Proteoform Atlas, a reference set which will be public and available to all, including the many proteomics companies recently advancing in the private sector. In order to develop this extensive, high-quality atlas, researchers must accelerate development of new, powerful, state-of-the-art technologies for deep proteoform analysis.
Kelleher said he hopes researchers, physicians, clinicians, scientists and engineers will help contribute to the global effort.
“With our global collaborators, we are excited to bring about the next generation of proteomics,” Kelleher said. “Defining the human proteome will allow us to really accelerate the pace of biomedical research and discovery.”
The study, “The Human Proteoform Project: Defining the human proteome,” was supported by the ALS Association (award number 508452), National Institutes of Health (award numbers R01 HL096971, GM117058, GM125085 and P41GM1085698), National Institute of General Medical Sciences (award numbers P41GM1085698and R35GM126914) and the U.S. Department of Energy (award number DE-FC02-02ER63421).
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Materials provided by Northwestern University. Original written by Amanda Morris. Note: Content may be edited for style and length.

Among their many extraordinary feats, some planarian flatworms reproduce by tearing off pieces of themselves to regenerate new worms. Now, researchers at the Stowers Institute for Medical Research have discovered that this process is controlled by Hox genes, a family of genes known to orchestrate important aspects of early development.
The finding, published online November 18, 2021, in Nature Communications, suggests a new role of these genes in adulthood. Hox genes continue to be expressed in adult tissues and are misregulated in certain human cancers, but their functional roles in these adult contexts are not well understood, according to lead author Christopher Arnold, PhD.
“By discovering new functions of Hox genes, we can begin to address the gap in our understanding of what these genes do in adult animals, both normally and in disease,” said Arnold, a postdoctoral scientist in the lab of Alejandro Sánchez Alvarado, PhD, Stowers executive director and chief scientific officer and Howard Hughes Medical Institute investigator.
Hox genes are arguably some of the most important genes in developmental biology. In multiple organisms, these genes have been shown to map out the body plan of the developing embryo along its anterior-to-posterior axis, or from head to tail. “But in our system, we had a puzzle because it seemed like none of the Hox genes played any role in flatworms,” said Arnold.
The asexual planarians (Schmidtea mediterranea) that the Sánchez Alvarado Lab studies have no embryonic stage — they are obligate adults, locked in a perpetual state of adulthood. And until recently, they appeared to lack the anatomical segments that Hox genes typically lay down to organize an organism’s body plan from end to end. However, in 2019 Arnold and his colleagues discovered that planaria were actually segmented. When the researchers squished the bodies of the tiny organisms with a cover slip, the flatworms popped apart into multiple, regularly spaced segments.
Because one of those segments precisely matched the piece that reproducing flatworms tear off when they propagate, the researchers suspected that Hox genes played a role in asexual reproduction. They inhibited the function of each of the Hox genes and then watched to see how those defects impacted the organism’s ability to perform reproductive acts in a dish.
Typically, when a flatworm reproduces asexually it begins by anchoring its tail to a solid substrate like an underwater rock or a petri dish. It then crawls in the opposite direction, undulating its midsection and stretching its body until finally it reaches a certain point where — like a rubber band — it breaks, leaving a small segment behind.
The researchers showed that five of the thirteen Hox genes were required for the worms to do the deed. They also discovered that two of these five genes had opposite effects on the segmentation and behaviors associated with asexual reproduction. Knocking down the Hox3 gene yielded worms with more head to tail segments that constantly tried to reproduce, whereas knocking down the post2b gene eliminated these segments and behaviors altogether.
“We had found that Hox genes were not only functioning in adult animals, but they were also required for an exclusively adult animal activity like asexual reproduction,” said Arnold. The researchers believe their findings indicate that many of the genes once thought to function only in embryonic development could also play important roles later in adult health and disease.
“It may be that our definition of what these genes are doing has been too narrow,” said senior author Alejandro Sánchez Alvarado. “There may be a lot more that we have not discovered yet, and we just need to look in the right place.” In the future, the team aims to study asexual reproduction in order to reveal new insights into the developmental programs underlying adult animal growth, behavior, and regeneration.
Other coauthors include Frederick G. Mann Jr., PhD, Stephanie H. Nowotarski, PhD, Julianna O. Haug, Jeffrey J. Lange, PhD, and Chris W. Seidel, PhD from the Stowers Institute and Analí Migueles Lozano from the University of Chicago.
The work was funded by the Howard Hughes Medical Institute, the Stowers Institute for Medical Research, and the National Institute of General Medical Sciences of the National Institutes of Health (award R37GM057260). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Previous research has found that chemotherapy can trigger muscle loss in people living with cancer, but a new study out of Penn State found it may also affect the way the body builds new muscle — and at lower doses than previously known, having potential implications for treatments and rehab programs.
According to the researchers, it was previously known that chemotherapy drugs can affect the mitochondria within cells, which can cause the loss of muscle tissue via a process called oxidative stress.
In their new study, the researchers studied three different chemotherapy drugs in cultured muscle cells at levels too low to trigger oxidative stress. They found that the muscle cells were still affected by the lower levels of drugs — this time by interfering with the process that builds muscle, called protein synthesis.
Gustavo Nader, associate professor of kinesiology, said that while the findings need to be confirmed in humans, they could have implications for cancer treatment in the future.
“Eventually, it may be that the implementation of cancer treatments should consider that even at low doses that do not cause oxidative stress, some chemotherapy drugs may still promote the loss of muscle tissue,” Nader said. “The tumor is already making you weak, it’s contributing to the loss of muscle mass, and the chemo drugs are helping the tumor to accomplish that.”
Additionally, Nader said the results — recently published in the American Journal of Physiology — Cell Physiology — also have the potential to change how health care professionals think about the ways chemotherapy affects the body.

The tapered cone shell is popular among seashell collectors for its colorful patterns, but the smooth mottled shells are also home to the cone snail which is capable of spewing a potent insulin-like venom that can paralyze its prey. Researchers at the University of New Hampshire have found that variants of this venom, known as cone snail insulin (Con-Ins), could offer future possibilities for developing new fast-acting drugs to help treat diabetics.
“Diabetes is rising at an alarming rate and it’s become increasingly important to find new alternatives for developing effective and budget-friendly drugs for patients suffering with the disease,” said Harish Vashisth, associate professor of chemical engineering. “Our work found that the modeled Con-Ins variants, or analogs, bind even better to receptors in the body than the human hormone and may work faster which could make them a favorable option for stabilizing blood sugar levels and a potential for new therapeutics.”
In their study, recently published in the journal Proteins: Structure, Function, and Bioinformatics, researchers looked more closely at the cone snail venom which induces a hypoglycemic reaction that lowers blood sugar levels. Unlike insulin made in the body, the venom’s peptide sequence — which allows it to bind to human insulin receptors — is much shorter. To test whether it would still bind effectively, the researchers used sequences of the insulin-like peptides in the venom of the cone snail C. geographus as a template to model six different Con-Ins analogs. The newly created variants were made up of much shorter peptide chains than human insulin — lacking the last eight residues of the B-chain of the human insulin.
To study the stability and variability of the new Con-Ins structures, they conducted multiple independent computer simulations of each Con-Ins variant complex with human insulin receptor in a near-physiological environment (accounting for water solvent, salinity of solution, temperature and pressure). They found that each insulin complex remained stable during the simulations and the designed peptides bound strongly — even better than the naturally occurring human insulin hormone. The interactions were then compared with the human insulin receptor and it was determined that each Con-Ins variant exhibits few feasible residue substitutions in human insulin.
“While more studies are needed, our research shows that despite the shorter peptide sequences, the cone snail venom could be a viable substitute and we are hopeful it will motivate future designs for new fast-acting drug options,” said Biswajit Gorai, postdoctoral research associate and lead author.
The insulin-like venom released by certain cone snails can be highly dangerous causing a hypoglycemic shock that immobilizes fish and potential prey. C. geographus has the most toxic sting known among the species and there have been reports of human fatalities, especially to unsuspected divers who are not aware of the snail’s venom.
Funding was provided by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R35GM138217. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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People with type 2 diabetes who contract COVID-19 are nearly 50% more likely to wind up in intensive care if they have poorly managed their blood sugar levels over the long-term than those with better long-term glycemic control, according to a study using anonymized health care data. The study, which looked at several potential impacts to COVID-19 severity among diabetics, also calculated a lower risk for patients using the common diabetes-control medication metformin, or a combination of metformin and insulin, or corticosteroids.
“We find that two- to three-year longitudinal glycemic levels better indicate the risk of COVID-19 severity than measurements which look at a shorter period of time,” said Deepak Vashishth, corresponding author, professor of biomedical engineering, and director of the Center for Biotechnology and Interdisciplinary Studies at Rensselaer Polytechnic Institute. “We hope these insights aid physicians in better treating and managing high-risk patients.”
“Evaluation and management of COVID-19-related severity in people with type 2 diabetes” looked at records for more than 16,000 people with type 2 diabetes and COVID-19 between 2017 and 2020, and was published in BMJ Open Diabetes Research & Care.
Type 2 diabetes patients are unable to regulate the amount of the sugar glucose in their bloodstream without medication and managing their diet. Chronic high blood-sugar levels, typically tracked as the percentage of hemoglobin A1c (HbA1c) found in the blood, can damage a variety of functions, including the circulatory, nervous, and immune systems.
Poor glycemic control creates a reaction that causes molecules known as advanced glycation end-products (AGEs) to accumulate, deteriorating the quality of bone over time, and Vashishth, an expert in bone, researches the impact of diabetes on bone. At the time the SARS-CoV-2 pandemic began, his research team was investigating whether measurements of longitudinal glycemic control — measures of blood-sugar levels averaged over two to three years — could provide a more accurate predictor of bone fracture risk among diabetics than the current standard predictor, which relies on measurements of bone mineral density.
AGEs are known to contribute to increased oxidant stress and inflammation, which are risk factors in COVID-19 and other respiratory illnesses. The team reasoned that the same longitudinal glycemic control measurement they were testing as a predictor of bone fracture risk might be useful in predicting the severity of COVID-19, said Bowen Wang, first author and a doctoral student in Vashishth’s lab.
Wang divided the records of type 2 diabetic patients in the study into two groups, those with “adequate” longitudinal glycemic control ranging from 6 to 9%, and those with “poor” glycemic control of 9% or above over two to three years. His analysis of the two groups revealed that those with poor glycemic control were 48% more likely to require treatment in an intensive care unit. By another measure, a 1% increase in longitudinal HbA1c is directly associated with a 12% increase in the risk of landing in the ICU.
Other statistically significant findings showed that diabetics who were taking metformin when they contract COVID-19 face a 12% lower risk of visiting the ICU, those on metformin and insulin have an 18% lower risk, and those prescribed corticosteroids have a 29% lower risk.
“People knew that diabetes was a risk factor for COVID-19-related outcomes, but not all diabetic patients are the same. Some people have a longer history of diabetes, some have more severe diabetes, and that has to be accounted for,” said Wang. “What this study does is to better stratify the level of diabetes within the population, so diabetic patients aren’t treated as a single population without any differences among them.”
Vashishth and Wang were joined on the research by Benjamin S. Glicksberg and Girish N. Nadkarni at the Icahn School of Medicine at Mount Sinai. Their work was supported by a grant from the National Institutes of Health.
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Materials provided by Rensselaer Polytechnic Institute. Original written by Mary L. Martialay. Note: Content may be edited for style and length.

When a muscle becomes injured, it repairs itself using a flurry of cellular activity, with stem cells splitting and differentiating into many types of specialized cells, each playing an important role in the healing process.
Biologists have struggled to study rare and transient muscle cells involved in the process, but Cornell engineers have lifted the curtain on these elusive dynamics with the launch of scMuscle, one of the largest single-cell databases of its kind.
A report on the work was published Nov. 12 in the journal Communications Biology. Co-senior authors are Ben Cosgrove and Iwijn De Vlaminck, both associate professors of biomedical engineering in the College of Engineering.
Recent advances in single-cell RNA sequencing allow biologists to identify tens of thousands of cells from a single tissue sample, but because muscle stem cells account for less than 1% of those cells — with their short-lived transient cell offspring being even more rare — sequencing experiments simply can’t capture the complete picture of muscle regeneration.
It’s a problem that Cosgrove ran into when he published a 2020 cell atlas containing 35,000 individual cells involved in the repair process. But of those cells, fewer than 200 of them were committed or fusing myogenic cells — the rare transient states that sequencing struggles to document.
“Imagine if you had a paint-by-numbers picture and you only colored in a quarter of the numbers,” said Cosgrove, who co-led the development of scMuscle along with De Vlaminck and doctoral student David McKellar. “We just couldn’t collect enough data ourselves to paint the whole picture of these subtle transitions as cells mature and specialize.”
The Cornell team knew there were other large sequencing datasets being developed, each capturing their own share of data. So, they used advanced computational techniques to start merging collections to paint the fuller picture. They combined 88 publicly available datasets with several of their own, leading to the scMuscle database, which houses the transcriptomic data from approximately 365,000 cells involved in muscle injury over a wide range of ages and experimental conditions.

To grow and spread, cancer cells must evade the immune system. Investigators from Brigham and Women’s Hospital and MIT used the power of nanotechnology to discover a new way that cancer can disarm its would-be cellular attackers by extending out nanoscale tentacles that can reach into an immune cell and pull out its powerpack. Slurping out the immune cell’s mitochondria powers up the cancer cell and depletes the immune cell. The new findings, published in Nature Nanotechnology, could lead to new targets for developing the next generation of immunotherapy against cancer.
“Cancer kills when the immune system is suppressed and cancer cells are able to metastasize, and it appears that nanotubes can help them do both,” said corresponding author Shiladitya Sengupta, PhD, co-director of the Brigham’s Center for Engineered Therapeutics. “This is a completely new mechanism by which cancer cells evade the immune system and it gives us a new target to go after.”
To investigate how cancer cells and immune cells interact at the nanoscale level, Sengupta and colleagues set up experiments in which they co-cultured breast cancer cells and immune cells, such as T cells. Using field-emission scanning electron microscopy, they caught a glimpse of something unusual: Cancer cells and immune cells appeared to be physically connected by tiny tendrils, with widths mostly in the 100-1000 nanometer range. (For comparison, a human hair is approximately 80,000 to 100,000 nanometers). In some cases, the nanotubes came together to form thicker tubes. The team then stained mitochondria — which provide energy for cells — from the T cells with a fluorescent dye and watched as bright green mitochondria were pulled out of the immune cells, through the nanotubes, and into the cancer cells.
“By carefully preserving the cell culture condition and observing intracellular structures, we saw these delicate nanotubes and they were stealing the immune cells’ energy source,” said co-corresponding author Hae Lin Jang, PhD, a principal investigator in the Center for Engineered Therapeutics. “It was very exciting because this kind of behavior had never been observed before in cancer cells. This was a tough project as the nanotubes are fragile and we had to handle the cells very gently to not break them.”
The researchers then looked to see what would happen if they prevented the cancer cells from hijacking mitochondria. When they injected an inhibitor of nanotube formation into mouse models used for studying lung cancer and breast cancer, they saw a significant reduction in tumor growth.
“One of the goals in cancer immunotherapy is to find combinations of therapies that can improve outcomes,” said lead author Tanmoy Saha, PhD, a postdoctoral researcher in the Center for Engineered Therapeutics. “Based on our observations, there is evidence that an inhibitor of nanotube formation could be combined with cancer immunotherapies and tested to see if it can improve outcomes for patients.”
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