Sight loss research needs urgent investment – The Guardian

January 7, 2020 medical

As leading ophthalmologists and researchers we are joining the eye research charity Fight for Sight to call for urgent action on blindness in 2020 to address the research funding gap.

We know that serious sight loss doesnt discriminate it can affect anyone at any time and it is on the increase. Science can already do so much and with the advent of new gene therapies and stem cell treatments we are so close to outcomes that were not possible a decade ago. Yet so much more needs to be done to develop new universal treatments.

The main barrier is the lack of research funding. It is unacceptable that in 2020 only 1% of UK grant funding goes to eye research, even though more than 20% of people will be affected by serious sight loss in their lifetime. Blindness can have a huge impact on peoples mental health and ability to work, increasing costs on health systems and infrastructure.

In 2019 the WHO and UN general assembly both outlined that globally more investment is needed into sight loss and research. We are calling for the new government and its partners to agree a national plan on sight loss and a research agenda that will help to ensure that eye research gets the funding it badly needs. Please join us at fightforsight.org.uk and let 2020 be the year that we accelerate progress in beating blindness.

Prof Chris Hammond Frost chair of ophthalmology, Kings College London, Prof Alan Stitt Dean of innovation and impact, Queens University Belfast, Prof Alastair Denniston Consultant ophthalmologist, Birmingham University, Prof Alison Hardcastle Professor of molecular genetics, UCL Institute of Ophthalmology, Prof Lynda Erskine Chair in developmental neurobiology, Aberdeen University, Prof Jeremy Guggenheim Director of research, Cardiff University, Prof David Steel Consultant ophthalmologist, Newcastle University, Prof Chris Inglehearn Professor of molecular ophthalmology and neuroscience, Leeds University, Prof Timothy Jackson Consultant ophthalmic surgeon, Kings College London, Prof Rachael Pearson Professor of developmental neuroscience, UCL Institute of Ophthalmology, Prof Jessica Teeling Professor of Experimental Neuroimmunology, University of Southampton, Prof Colin Willoughby Professor of ophthalmology, Ulster University

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Sight loss research needs urgent investment - The Guardian

Cell Biology

Discovery of cellular ‘hands’ could have implications in the fields of cell, developmental biology – News-Medical.net

January 7, 2020 medical

The protein, called syndecan-4, combines with fellow cell membrane proteins, called integrins, to form protruding 'hands' that sense the environment outside the cell.

Both proteins sit in the cell membrane, with one end pointing inside the cell and the other outside. They are therefore in a prime position to sense conditions outside the cell and convert signals to biochemical messages that change conditions inside the cell. In doing so, they're able to drive some of the cellular processes behind cancer and other diseases.

The early-stage research, conducted by a team at Imperial College London, Queen Mary University of London, and Tampere University in Finland, could present a new research pathway and drug target for certain cancer types.

Lead researcher Dr Armando del Ro Hernndez, of Imperial's Department of Bioengineering, said:

Our findings could have immediate implications in the fields of cell and developmental biology, and lead to developments in several diseases including cancer and fibrosis."

The paper is published today in Nature Materials.

Syndecan-4 exists in nearly every human cell and is already known for its role in cardiovascular disease. However its potential roles in cancer biology and drug development have thus far been overlooked.

To study syndecan-4 the research team, led by Dr del Ro Hernndez, used biophysical, cell biology, and computational techniques.

The team found that activating these cellular 'hands' triggers a pathway with key roles in disease development, involving a cellular protein called the yes-associated protein (YAP).

YAP triggers some of the typical hallmarks of cancer. It reduces cells' ability to program their own death, in a process called apoptosis. Cells initiate apoptosis when they age or malfunction, so halting apoptosis allows diseased, even cancerous, cells to spread. YAP also controls the development of blood vessels - a hallmark of cancer as tumor growth requires extra blood flow.

They also found that syndecan-4 helps cells respond to movements outside themselves, by creating tension in the cytoskeleton - the 'scaffolding' within cells. This makes cells stiffen, which activates an enzyme called PI3K that regulates additional hallmarks of cancer.

It does this by converting the movements outside the cell into biochemical signals which, the researchers found, 'tune' the way the cells respond to tension and movement.

Dr del Ro Hernndez said: "The way cells interact with their environment could inform how we engineer tissues and mimic human organs for drug design. Syndecan-4 could now play a fundamental part in this endeavor."

Co-lead author Dr Stephen Thorpe of Queen Mary University of London said:

As syndecan-4 is expressed on almost all of our cells, the mechanisms we've uncovered could be targeted to alter any number of diseases and biological processes."

Professor Vesa Hytnen of Tampere University said: "Better understanding of cellular mechanosensing opens possibilities to develop treatments for conditions like cancer and fibrosis."

Next, the research team will further investigate syndecan-4's links to specific diseases like pancreatic cancer.

Dr del Ro Hernandez said:

Our next approach will involve syndecan-4 as a key contributor in disease. We hope this will lead to new insights into disease mechanisms."

Cell Biology

Fitzpatrick elected to microscopy society governing council – Washington University School of Medicine in St. Louis

January 7, 2020 medical

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Noted for his expertise in cellular imaging, 3D microscopy

Fitzpatrick

James Fitzpatrick, PhD, a professor of neuroscience and of cell biology and physiology at Washington University School of Medicine in St. Louis, has been elected biological sciences director of the Microscopy Society of America. He will serve a three-year term on the societys governing council beginning in 2020.

An expert in biological imaging, Fitzpatrick is the director of the Washington University Center for Cellular Imaging. The center boasts 16 state-of-the-art light, X-ray and electron microscopes including a 300kV Titan Krios cryo-electron microscope and provides imaging expertise and support to researchers at the university and elsewhere.

Fitzpatricks research is focused on developing ways to correlate microscopy using charged particles such as electrons or ions with light microscopy of the same sample. By combining the advantages of charged-particle microscopy methods which generate finely detailed grayscale images at nanoscale resolution and light microscopy which uses color-coded labels to flag molecules or internal cellular structures of interest Fitzpatrick aims to advance our understanding of biological processes in human health and disease. He also is working to use artificial intelligence methods to develop new tools to visualize and manipulate image data obtained from different techniques.

The Microscopy Society of America is dedicated to the promotion and advancement of techniques and applications of microscopy and microanalysis in relevant scientific disciplines. Fitzpatrick plans to use his position on the societys governing council to increase trainee engagement with the society, cultivate mentorship opportunities for early-career scientists and advocate for increased diversity in the community.

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Fitzpatrick elected to microscopy society governing council - Washington University School of Medicine in St. Louis

Cell Biology

Vapers Reported Adverse Health Effects Online for Years: Study – The Scientist

January 7, 2020 medical

An analysis of language on an electronic cigarette users online discussion forum shows vapers reported adverse health effects online for at least seven years, long before vaping-associated pulmonary illness, or VAPI, was recognized by the medical community last summer, researchers reported January 3 in the Journal of Medical Internet Research.

The sudden uptick in symptoms and conditions related to VAPI comes at least 10 years after e-cigarette products gained widespread popularity in the United States, including the rise in popularity of JUUL and marijuana vape products, Prue Talbot, a professor of cell biology at the University of California, Riverside, who led the research, says in a media release. Our data, which shows many of the symptoms characterizing the current patients have been reported online for at least seven years, suggests cases similar to those in the current VAPI epidemic have existed previously and been unreported or simply not linked to vaping.

To conduct the study, Talbot and her team collected information from an e-cigarette forum posted between January 2008 and July 2015 and used a web crawler to analyze the language to evaluate the health effects of vaping. Of the 41,000 posts analyzed, 17 percent mentioned positive health effects, 38 percent were neutral, and 45 percent mentioned negative health effects. Although positive symptoms were not frequently reported in the forum, some individuals did mention reduced tiredness, insomnia, and wheezing, while the negative health effects included headache, throat pain, coughing, itching, and uneasiness, similar to some of the symptoms listed for VAPI.

Our data underscore the idea that e-cigarette use is not free of adverse health effects and suggest that the epidemic we are seeing now will continue to grow given the many reports in the forum of symptoms characteristic of VAPI, My Hua, a graduate student in Talbots lab, says in the release. It is important that vigilant reporting of cases, tracking symptoms, and engaging in research on the health effects related to e-cigarette use be continued and expanded to understand and contain VAPI.

Ashley Yeager is an associate editor atThe Scientist. Email her atayeager@the-scientist.com. Follow her on Twitter@AshleyJYeager.

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Vapers Reported Adverse Health Effects Online for Years: Study - The Scientist

Cell Biology

Where Are They Now? Top 3 Biotech Startups From NextGen Bio Class of 2018 – BioSpace

January 7, 2020 medical

Every year, BioSpace analyzes the biotech industry, looking for the hot new biotech startups to watch. We then produce the NextGen Bio Class of, twenty companies ranked based on several categories, including Finance, Collaborations, Pipeline, and Innovation. The companies were typically launched no more than 18 months before the list was created.

We thought it would be insightful to look back at our previous lists to see where some of those companies are today. Heres a look at the top three companies from the Top 20 Life Science Startups to Watch in 2018.

#1. BlueRock Therapeutics. Founded in 2016, BlueRock was #1 on our list of companies to watch in 2018. With facilities in Ontario, Canada; Cambridge, Massachusetts; and New York, New York, BlueRock launched in December 2016 with a $225 million Series A financing led by Bayer AG and Versant Ventures. The company focuses on cell therapies to regenerate heart muscle in patients who have had a heart attack or chronic heart failure, as well as therapies for patients with Parkinsons disease.

In October 2017, BlueRock and Seattle-based Universal Cells entered into a collaboration and license deal to create induced pluripotent stem (iPS) cell lines that can be used in the manufacture of allogeneic cellular therapies. Shortly afterwards, the company established its corporate headquarters in Cambridge, and in April 2018, established a research-and-development hub in New York City, as well as formalizing a sponsored research collaboration with the Center for Stem Cell Biology at Memorial Sloan Kettering (MSK) Cancer Center. The collaboration focuses on translating Ketterings expertise in creating multiple types of authentic neural cells from stem cells to address diseases of the central and peripheral nervous system. BlueRock also received $1 million from the State of New York and Empire State Development under its economic development initiatives program.

In April 2019, BlueRock partnered with Editas Medicine (which was on BioSpaces NextGen Bio Class of 2015 list) to combine their genome editing and cell therapy technologies to focus on novel engineered cell medicines. Part of the deal was to collaborate on creating novel, allogeneic pluripotent cell lines using a combination of Editas CRISPR genome editing technology and BlueRocks iPSC platform.

And finally, in August 2019, Bayer AG acquired BlueRock for the remaining stake in the company for about $240 million in cash and an additional $360 million in pre-defined development milestones.

#2. Prelude Fertility. Prelude Fertility is a bit of an outlier from the typical BioSpace NextGen company, because it isnt quite a biopharma company. It is a life sciences company whose business model is aimed at in vitro fertilization and egg freezing. It was founded with a $200 million investment by entrepreneur Martin Varsavsky. The investment was in the largest in vitro fertilization clinic in the Southeast, Reproductive Biology Associates of Atlanta, and its affiliate, My Egg Bank, the largest frozen donor egg bank in the U.S.

Since then it has expanded in various parts of the country, including adding San Francisco-based Pacific Fertility Center (PFC) to its network in September 25, 2017; partnering with Houston Fertility Institute and acquiring Vivere Health; partnering with the Advanced Fertility Center of Chicago; and in October 2018, partnered with NYU Langone Health.

In March 2019, Prelude merged with Inception Fertility to establish the Prelude Network as the fastest-growing network of fertility clinics and largest provider of comprehensive fertility services in the U.S. Inception is acting as the parent company, with the Prelude Network, both having board representatives from the previous organizations.

#3. Relay Therapeutics. Ranking #3 on our list for 2018, Relay Therapeutics launched in September 2016 with a $57 million Series A financing led by Third Rock Ventures with participation form D.E. Shaw Research. On December 14, 2017, it closed on a Series B round worth $63 million, led by BVF Partners, with new investors GV (formerly Google Ventures), Casdin Capital, EcoR1 Capital and Section 32.

The company focuses on the relationship between protein motion and function. It merges computational power with structural biology, biophysics, chemistry and biology. In December 2018, the company completed a $400 million Series C financing. It was led by the SoftBank Vision fund and included additional new investors, Foresite Capital, Perceptive Advisors and Tavistock Group. Existing investors also participated.

The company announced at the time it planned to use the funds to accelerate the implementation of its long-term strategy, expanding its discovery efforts, advancing existing programs into the clinic and improving its platform.

Cell Biology

Mitochondrial Division in the Cell Is Common in Primitive and Advanced Species on Earth – Science Times

January 7, 2020 medical

(Photo : inteng-storage.s3.amazonaws.com)There is evidence that points out that mitochondria division shared by both primitive and advanced species living today.

All living things are born out from a cell, and thus began the hot pools where the cauldrons of creation cooked up the first batches of life. It was like a cook in the kitchen throwing in everything needed to complete the first cell. From this simple amoeba, the process ofmitochondrial divisionthat lives on to this day had started. All creature, living or extinct, primitive and advanced, have inherited this cellular mechanism from the first one-celled creature ever created.

The question about how everything ties up to the living "multi-cell scientist" or the "single-celled organisms"gave birth to the concept that everything is related to the simplest "amoeba" or "protozoan". This evolutionary process has been passed and tossed all over, resulting in the belief that it might be the same for other exo-species on other planets.

Tying up the loose ends for lower to higher animals is the"endosymbiotic theory",the keyword is endo- which is inside and symbiotic which refers to the connection to something. With the endosymbiotic theory, scientists state that advanced multi-cell animal, including homo sapiens, are "eukaryotes", while single-celled creatures are "prokaryotes". Both eukaryotes and prokaryotes related to the endosymbiotic theory, and science has come up with enough evidence to support it.

According to the study, all living creatures undergo a process of energy production in their cells. With themitochondria in the cells poweringupthe division of cells, production of enzymes and chemicals happen and it keeps animals alive. This is much like a mini-factory inside so many cells that create power for adaption and evolution that led to what life there is right now. The "mitochondria" is something like a gift from these creatures' "prokaryotic ancestors" which made evolution possible.

With the knowledge that all creatures have the ancient "mitochondria" inside, the next question is how similar are advanced and primitive species. Finding the secret, how the mitochondria exactly work, is what scientists need to know. It is Pandora's box of secrets that will open a new age of knowing more about the cellular biology of every living thing today.

To probe further, scientists at the Tokyo University of Science, headed bySachihiro Matsunagadid research on "mitochondria" with red algae. To make it easier, the group used it because it had one mitochondrion only. One result that shows promise, is when proteins were phosphorylated by Aurora kinase that produced "dynamin". Later on, other experiments carried out in a human cell had the same result, and "dynamin" was found too.

The experiment proved there is indeed a connection from the Red algae to a complex human. Finding "dynamin" as a regulator of mitochondria division is an incredible find for the Japanese researchers. The impact of the result is impressive, which sheds light why mitochondria division is critical to all species from primitive to advanced.

Related Article: Breakthrough in Understanding Evolution - Mitochondrial Division Conserved Across Species

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Mitochondrial Division in the Cell Is Common in Primitive and Advanced Species on Earth - Science Times

Cell Biology

Trinity Biology Professor and Alumni Co-Author Paper Published in International Scientific Journal – Trinity College

January 7, 2020 medical

Research by Trinity College Professor of Biology Kent Dunlap and two of his former students was published last month in one of the worlds oldest scientific journals, the London-based Proceedings of the Royal Society B.

The paperwhich Dunlap co-authored with research students Josh Corbo 19 and Margarita Vergara 19, along with collaborators from the University of Texas at Arlingtonreports that killifish in Trinidad that live with predators in their environment grow more brain cells than those that face no predators. The study was highlighted recently by the science and technology magazine New Scientist.

The researchers studied the brains of fish that are separated into distinct populations by waterfalls along streams. The killifish living downstream live among predatory fish, while the fish upstream do not, said Corbo, who double-majored in biology and philosophy at Trinity and is now a Cancer Research Training Award (CRTA) Fellow at the National Cancer Institute. Our central question was: how does negative stimulipredationin the environment affect the rate of brain cell proliferation? The implication of our research reaches much farther than the Northern Mountain Range of Trinidad. The topic of how the environment we live in affects our health concerns many disciplines, from public health to sociology. Our research draws more attention to our understanding of the relationship we as organisms have with our environment.

Dunlap first traveled to Trinidad with the colleges Trinity in Trinidad program and found the freshwater killifish to be a good subject for his work on brain cells. The Dana Foundation supported my research and the Trinity in Trinidad program was very helpful with the logistics, said Dunlap, who has previously researched the production of brain cells in electric fish. When Dunlap brought specimens back to campus to study, Corbo and Vergara got to work. They were motivated, engaged students who really took ownership in the lab and were excellent lab scientists, Dunlap said. They were curious and capable and a delight to work with.

Vergara, who completed a major in biology and a minor in Italian at Trinity and is now earning a masters in clinical embryology at the University of Oxford, said that she and Corbo sectioned brain tissues and conducted a procedure called immunohistochemistry to quantify the formation of new brain cells. Professor Dunlap also allowed us to revise and provide constructive feedback for the manuscriptthat was submitted for publication, Vergara said.

Corbo added, It was a great experience to see a paper from start to finish as an undergraduate, as such an experience is usually gained while in graduate school. Corbo spent a summer working in the lab through Trinitys Summer Research Program and now attributes much of his ability as a researcher to the skills he learned as an undergraduate research student. Professor Dunlap emphasized that your research will not matter if you cannot talk about it. Nothing has been truer, Corbo said. During lab meetings, we would have random research presentations for which he would decide who the audience was; it could be a novice, a biology student, or an expert in the field. The task was to present your research in the most clear and concise manner. That was the most important lesson I learned during my time in the lab.

Trinity students have the opportunity to begin research work early in their undergraduate careers and build strong connections with faculty members. Vergara, who first worked in Dunlaps lab as a sophomore, said, I believe that the most valuable benefit of conducting research as an undergraduate is not only the practical skills that you learn along the way, but the relationships that you get to establish with your professor and lab mates. Professor Dunlap also supervised my thesis project, became a real mentor who advised me when I needed to make important career decisions, and taught me lessons that will always stay with me after graduating from Trinity.

For Vergara, the experience of working on research with Dunlap sharpened her problem-solving skills, strengthened her proficiency as an academic writer and critical thinker, and allowed her to develop new technical expertise. More importantly, she said, it allowed me to gain a balance between independence and collaboration. I learned the importance of asking questions, making decisions as a group, and communicating findings. The research assistantship provided me with a solid foundation for the challenges and tasks that I am now undertaking in graduate school.

Read the full paper co-authored by Dunlap and the Trinity alumni in the Proceedings of the Royal Society B here. Proceedings is the Royal Societys flagship biological research journal, dedicated to the worldwide dissemination of high-quality research. It publishes original articles and reviews of outstanding scientific importance and broad general interest. The main criteria for acceptance are that a study is novel and has general significance to biologists.

Cell Biology

Foundation Supports New Work on Brain-eating Amoeba – UMass News and Media Relations

January 7, 2020 medical

Evolutionary cell biologist Lillian Fritz-Laylin, biology, recently was granted a three-year, $300,000Smith Family Award for Excellence in Biomedical Researchto support her research on the pathogenesis of the brain-eating amoebaNaegleria fowleri. The amoeba gets inside swimmers noses, crawls up the olfactory nerve and into the brain where they destroy tissue.

As she explains, Although this amoeba has killed 95% of the people its infected, we know almost nothing about it. She and colleagues use the non-pathogenic sister species Naegleria gruberias a practical and safe study organism for understanding the basic biology of these species, in particular, how the cells move.

Fritz-Laylin adds, There are a lot of species of Naegleria, but only one causes disease, so there has been a lot of focus on that, but when treating the disease what really matters is how to kill Naegleria without hurting our own cells. Well be looking into ways to do that. Our human cells use two different polymer systems to move, but these amoeba use only one of them, so that difference could be a target for treatment.

Katrina Velle, a postdoctoral researcher in the Fritz-Laylin lab one of the few to study this organism, she notes will continue to lead the project and conduct much of the planned experimental and genomic work. Using gene manipulation, genomics techniques, treatment with various compounds and inhibitors, they will study how the organisms move, eat, divide and maintain their water balance.

We might be able to interrupt any one of these systems to kill them without hurting the person infected, Fritz-Laylin points out.

Much of her research has been focused on the evolution of cell movement, she notes, explaining that humans and Naeglaria shared a common ancestor about 1.2 billion years ago. The amoeba, which can either crawl or swim at different life cycle stages, evolved movement that looks similar to that of human white blood cells, but the underlying systems are very different; similar functions evolved along different pathways.

Human white blood cells are immune system scavengers that rove through the bloodstream eating invading pathogens. Fritz-Laylin explains, They eat bacteria, so they crawl around to hunt them. If you look in a microscope, Naeglaria move like our white blood cells but they achieve that movement differently.

For 28 years, the Smith Family Foundation has supported full-time faculty biomedical researchers at nonprofit academic, medical or research institutions in Massachusetts, at Brown University or at Yale University. Its mission is to launch the careers of newly independent biomedical researchers with the ultimate goal of achieving medical breakthroughs.

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Foundation Supports New Work on Brain-eating Amoeba - UMass News and Media Relations

Cell Biology

Silicon Therapeutics Expands Leadership Team with Key Appointments in Clinical Development and Strategy as well as Computational Physics – Business…

January 7, 2020 medical

BOSTON--(BUSINESS WIRE)--Silicon Therapeutics today announced three additions to its management team to help lead the company through its next stage of growth. Humphrey Gardner, MD, FCAP has joined the company as Chief Medical Officer; Christopher Borella, PhD, has joined as Vice President, Head of Operations; and Huafeng Xu, PhD, has joined as Chief Technology Officer.

"The appointments of Humphrey and Chris, who bring deep expertise in clinical development and strategy, reflect the progress we have made in building and advancing our oncology pipeline, said Lanny Sun, Silicon Therapeutics Co-founder and CEO. They will play key roles as our lead STING agonist enters clinical trials and our other programs advance towards the clinic. Huafeng will strengthen our leadership in computational physics, bringing over 15 years of experience in methods and theory development.

Dr. Gardner joins Silicon from Evelo Biosciences, where he served as Chief of Medical Oncology and led oncology discovery as well as the IND and clinical development of their first microbial cancer immune therapy. Previously, he served as Vice President of Early Clinical Development in both Infection and in Oncology at AstraZeneca, and as Senior Vice President of Clinical Development at Karyopharm. Prior to these appointments, he led the Oncology Translational Laboratories at Novartis, and various discovery and translational programs at Biogen. Before joining industry, Dr. Gardner was an Assistant Professor of Cell Biology at The Scripps Research Institute. Dr. Gardner obtained his BA in Biochemistry and his MB, BChir, at the University of Cambridge, UK. He did his specialty training in anatomic pathology at the Beth Israel Hospital, Harvard Medical School. He completed his postdoctoral fellowship at the Whitehead Institute in the laboratory of Professor Rudolf Jaenisch. Dr. Gardner has over 100 publications and patents in fields including oncology, neuroscience, rheumatology, and diagnostics.

Dr. Borella joins Silicon Therapeutics from Agios Pharmaceuticals where he was the Head of Early Stage Program Management and Project Leader for their MAT2A franchise. During his 8+ years at Agios, Chris and his team were directly involved in bringing seven drug candidates including two marketed drugs, Tibsovo (ivosidenib) and Idhifa, (enasidenib) forward into the clinic. Prior to Agios Therapeutics, Dr. Borella held project leadership positions at both Proteostasis and Synta Pharmaceuticals. He received his PhD in Medicinal Chemistry from Stony Brook University and was a post-doctoral fellow at Memorial Sloan Kettering Cancer Center.

Dr. Xu joins Silicon Therapeutics after 12 years at D. E. Shaw Research, the leading institution in method and hardware development for molecular simulations, where he played an early role in designing the specialized Anton chip for molecular dynamics simulations, and he led the development of the methods and software for free energy calculations that are now widely used in the pharmaceutical industry. He has also pioneered the application of long-timescale molecular simulations and statistical mechanical theory in revealing fundamental mechanisms of molecular recognition in immunology and virology. Dr. Xu started his career in the biotechnology industry at 3-Dimensional Pharmaceuticals. He earned his Bachelor of Science from Peking University and his M.S. and Ph.D. degrees from Columbia University. He was a visiting postdoctoral scholar in University of California, San Francisco.

About Silicon Therapeutics

Silicon Therapeutics (SiTX) is a physics-driven drug discovery company focused on small molecule therapeutics for cancer that target innate immunity to light the spark within immunologically cold tumors. The companys unique computational physics-based platform can accurately simulate the physical motion and properties of biological targets at atomistic resolution to reveal unique insights into the drug design process. The platform is cohesively integrated with a world-class wet lab including biophysics, chemistry, and biology to enable rapid hypothesis-driven data generation to advance drug discovery projects on targets that have traditionally been thought of as undruggable. The SiTX lead program is a small molecule STING agonist for systemic delivery in I/O that is slated to enter the clinic in mid-2020.

Learn more at http://www.silicontx.com

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Silicon Therapeutics Expands Leadership Team with Key Appointments in Clinical Development and Strategy as well as Computational Physics - Business...

Cell Biology

Advanced imaging tips T cell target recognition on its head – Mirage News

January 7, 2020 medical

A team of leading Australian scientists have published research which transforms existing perceptions of T cell recognition.

T cells represent a key component of our immune system, and play a critical role in protecting us against harmful pathogens like viruses and bacteria, and cancers. The more we understand about how they recognise, interact with and even kill infected or cancer cells moves us closer to developing therapies and treatments for a range of conditions.

In a paper published today in the premier international journal Science, an Australian team of scientists led by Monash University, Hudson Institute of Medical Research, the Australian Research Council Centre of Excellence in Advanced Molecular Imaging and the University of Melbourne at the Doherty Institute, has redefined what we thought we knew about T cell recognition for the past 20 years.

Hudson Institutes Dr Edward Giles (Honorary Clinical Associate in Regulation of Interferon and Innate Signalling) provided valuable clinical contribution towards the study.

It was great to be able to contribute to this ground-breaking work on T cell recognition said Dr Giles.

Through a clinical collaboration, we were able to show this new immune interaction in the gut, and suggest a role in coeliac disease. Coeliac disease is an immune-mediated disease affected up to 1 in 70 Australians, and its only treatment is a lifelong strictly gluten-free diet. This new work opens potential new targets for treatment, as well as a deeper understanding of how the immune system recognises targets in the gut and elsewhere.

In order to interact with other cells in the body, T cells rely on specialised receptors known as T Cell Receptors (TCRs) that recognise virus or bacteria fragments that are bound to specialised molecules called major histocompatibility complex (MHC) or MHC-like. Over the past 20 years, the prevailing view was that TCRs sat atop the MHC and MHC-like molecules for recognition.

The team of scientists characterised a new population within a poorly understood class of T cells called gamma delta T Cells that can recognise an MHC-like molecule known as MR1.

Using a high intensity X-ray beam at the Australian Synchrotron, the scientists obtained a detailed 3D image of the interplay between the gamma delta TCR and MR1 revealing an intriguing result whereby the gamma delta TCR-bound underneath the MHC-like molecule for recognition.

This highly unusual recognition mechanism reshapes our understanding of how TCRs can interact with their target molecules, and represents a major development in the field of T cell biology.

Think of it like a flag attached to a cell. We always thought the T cells were coming along and reading that flag by sitting atop it. We have determined that instead, some T cells can approach and interact with it from underneath, said Dr Jrme Le Nours from Monash Biomedicine Discovery Institute, co-lead author on the paper.

These are the types of fine and important details that can change how we approach future research avenues in T cell biology, said Dr Le Nours.

This is important because T cells are a critical weapon in our immune system, and understanding how they target and interact with cells is crucial to harnessing their power in therapies such as infection and cancer immunotherapy.

Our study shows that MR1 is a new type of molecular target for gamma delta T cells. These cells play a decisive role in immunity to infection and cancer, yet what they respond to is poorly understood. MR1 may be signalling to gamma delta T cells that there is a virus, or cancer cell and triggering these cells to initiate a protective immune response said Dr Nicholas Gherardin from the Doherty Institute, co-lead author on the paper.

Were very excited to follow up these findings in studies that will aim to harness this new biology in disease settings.

The research findings were a culmination of a six-year project that involved collaborative support from Australian scientists, the ARC Centre of Excellence in Advanced Molecular Imaging, the use of the Australian Synchrotron, and funding from the National Health and Medical Research Council and the Australian Research Council.

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Advanced imaging tips T cell target recognition on its head - Mirage News