Category Archives: Cell Biology

Cell Biology

Bruker : partners with ANPC to support major new frontline response to combat the COVID-19 threat – Marketscreener.com

04/11/2020 | 07:43am EDT

Bruker partners with ANPC to support major new frontline response to combat the COVID-19 threat

Bruker is proud to partner with Australian National Phenome Centre (ANPC) at Murdoch University to support the work of their researchers into the COVID-19 pandemic threat.

The ANPC team, led by world-renowned phenomics pioneer and academician Professor Jeremy Nicholson, and working with the South Metropolitan Health Service COVID-19 Response Team and the broader Western Australian (WA) healthcare community, has launched a major research and diagnostics project to better understand and predict variation in COVID-19 severity and determine the complex genetic, environmental and lifestyle interactions that influence its pathogenicity in individuals. Later they will engage with clinical trials of novel antiviral agents and when available vaccines in order to predict responder/non-responder outcomes.

Accelerating time to diagnosis

The goal is to deliver diagnostic and prognostic solutions in an accelerated time-frame. Most importantly, the risk of severity of infected patients needs to be assessed rapidly to help guide and optimize the clinical patient pathway. Researchers at the ANPC will use a range of state-of-the-art Avance IVDr nuclear magnetic resonance (NMR) and timsTOF Pro Impact II and Solarix MR mass spectrometry (MS) instrumentation from Bruker, as well as data modeling approaches, to perform broad and deep metabolic analysis of the molecular, physical and biochemical characteristics of blood plasma and urine samples to create informative translational models. These models will predict variation in the severity of the disease and help understand differential responses to therapeutic interventions.

Professor Nicholson said: 'At the ANPC, we are dedicating 100% of our resources to the COVID-19 fight for at least a year. This is the greatest emergent healthcare challenge on the planet and there is no better equipped metabolic lab in Australia, or possibly anywhere in the world, to undertake this type of investigative work in an excellent clinical and hospital framework.

'Linked to our genomics team, led by Professor Simon Mallal and Associate Professor Mark Watson, we're setting out to identify specific biomarkers of the disease to figure out who has it, how we can detect it and stratify patients by severity risk, and assess the real time patient responses to treatments.':

Scientific partnership to drive clinical research

Frank H. Laukien, Ph.D, President and CEO of Bruker Corporation, commented: 'We are strongly committed to supporting Professor Nicholson and his team scientifically and technically. The comprehensive COVID-19 clinical research plan at Murdoch University into metabolic biomarker patterns of diseases, prognosis, and treatment response is exceptional.

'In particular, I hope that the team can find evidence-based clinical protocols very soon to reduce mortality in 'phase 2' of COVID-19 with its life-threatening lower respiratory tract infections. Medical science needs to determine urgently whether broad spectrum antibiotics and/or immunosuppressants improve survival statistics in 'phase 2', when viral pneumonia, potential bacterial pneumonia or ventilator-associated pneumonia (VAP), as well as lung inflammation due to our own immune systems' cytokine storms, appear to create a very dangerous set of co-morbidities.'

Unique bio sample collection capability

The project will see the ANPC working hand-in-hand with Professor Merrilee Needham of Murdoch University and Notre Dame University, and Professor Toby Richards of the University of Western Australia, who are bringing together the top doctors and researchers from WA through the Western Australian Health Translation Network (WAHTN) led by Professor Gary Geelhood for the COVID-19 Response Team.

It is anticipated that all new COVID-19 patients will be consented for testing on admission and later for clinical trials, with the ANPC running the samples from those trials and tests, including longitudinal urine and plasma metabolic monitoring.

Commenting on the unique position of the WA-based research team, Professor Richards said: 'We are in the second wave and have the opportunity to be prepared for COVID-19. We have built a unique platform in WA to collect patient data and bio samples to enable a thorough understanding of the disease and response to treatment.'

Mitigating current and future threats

Understanding the pathways to infection and the biological consequences will enable the development of effective treatments and vaccines to mitigate the current threat to thousands of people across the world. This pioneering work will also prepare us for the threat of viral pandemics in the future.

About the Australian National Phenome Centre

The Australian National Phenome Centre (ANPC), led by Murdoch University, will transform how long and how well people live, not just in Australia, but around the world. The work of the ANPC supports almost every area of bioscience. It reaches across traditional research silos and fosters a new, more collaborative approach to science. Long-term, the ANPC hopes to build 'global atlases' of human disease, providing insights into future health risks which everyone on the planet can benefit from. The only facility of its kind in the southern hemisphere, the ANPC brings together all five Western Australian universities and leading health and medical research institutes. It is linked to the International Phenome Centre Network and also has wide applications in agriculture and environmental science. The ANPC positions Perth and WA as a global leader in precision medicine, and enables quantum leaps in predicting, diagnosing and treating disease. It is part of the Health Futures Institute at Murdoch University.

Technology and partners

The ANPC is equipped with multiple state-of-the-art nuclear magnetic resonance (NMR) and mass spectrometry (MS) instruments from ANPC strategic alliance partners Bruker BioSpin and Bruker Daltonics. Bruker is a manufacturer of scientific instruments for molecular and materials research, as well as for industrial and applied analysis.

Phenomes

A person's phenome is a dynamic fingerprint of their unique biology resulting from the complex interactions between environmental and genetic factors. Phenomics is the study of how the environment and a person's lifestyle interacts with their genes to influence their health and risk of disease. Metabolic phenotyping is the analysis of biological tissue and fluid to uncover the specific interactions of genetic, environmental and lifestyle factors at a molecular level.

The team

Professor Jeremy Nicholson

An internationally renowned pioneer in metabolic phenotyping and systems medicine, Professor Nicholson leads the ANPC. He currently holds the appointment of Pro Vice Chancellor for the Health Futures Institute at Murdoch University. Professor Nicholson is a Highly Cited Scholar who has published more than 800 peer-reviewed papers on molecular aspects of body systems medicine. A Fellow of the UK Academy of Medical Sciences, Professor Nicholson comes to WA from Imperial College London where he was the founding director of the MRC-NIHR National Phenome Centre and previously Head of Surgery and Cancer. He is currently an Emeritus Professor of Biological Chemistry at Imperial College London.

Professor Elaine Holmes

Another systems medicine pioneer, Professor Holmes is a Highly Cited Scholar and a Fellow of the UK Academy of Medical Sciences. Professor Holmes also comes to WA from Imperial College London where she was previously Head of the Division of Computational and Systems. She is Professor of Computational Medicine and a Premiers' Fellow, Australian National Phenome Centre, Murdoch University She also holds a current appointment at Imperial College London as Professor of Chemical Biology.

Dr Ruey-Leng Loo

Premier's Intermediate Fellow, Senior Lecturer, ANPC, Murdoch University.

Professor Toby Richards

Michael Lawrence Brown Chair of Surgery UWA, Honorary Professor Institute of Clinical Trial Methodology University College London, Director COVID Research Response.

Professor Merrilee Needham

Senior Consultant, Director of Research, Fiona Stanley Hospital, Murdoch University & University of Notre Dame Australia.

About Bruker Corporation

Bruker is enabling scientists to make breakthrough discoveries and develop new applications that improve the quality of human life. Bruker's high-performance scientific instruments and high-value analytical and diagnostic solutions enable scientists to explore life and materials at molecular, cellular and microscopic levels. In close cooperation with our customers, Bruker is enabling innovation, improved productivity and customer success in life science molecular research, in applied and pharma applications, in microscopy and nanoanalysis, and in industrial applications, as well as in cell biology, preclinical imaging, clinical phenomics and proteomics research and clinical microbiology.

Disclaimer

Bruker Corporation published this content on 11 April 2020 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 11 April 2020 11:42:05 UTC

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Bruker : partners with ANPC to support major new frontline response to combat the COVID-19 threat - Marketscreener.com

Cell Biology

UK Prime Minister Boris Johnson hospitalized with virus – The Republic

LONDON British Prime Minister Boris Johnson was admitted to a hospital Sunday for tests, his office said, because he is still suffering symptoms, 10 days after he was diagnosed with COVID-19.

Johnsons office said the admission to an undisclosed London hospital came on the advice of his doctor and was not an emergency. The prime ministers Downing St. office said it was a precautionary step and Johnson remains in charge of the government.

Johnson, 55, has been quarantined in his Downing St. residence since being diagnosed with COVID-19 on March 26 the first known head of government to fall ill with the virus.

Johnson has continued to preside at daily meetings on Britains response to the outbreak and has released several video messages during his 10 days in isolation.

In a message Friday, a flushed and red-eyed Johnson said he said he was feeling better but still had a fever.

The virus causes mild to moderate symptoms in most people, but for some, especially older adults and the infirm, it can cause pneumonia and lead to death.

U.S. President Donald Trump offered encouragement to Johnson as he opened a White House briefing on the pandemic Sunday. All Americans are praying for him, Trump said.

Johnson has received medical advice remotely during his illness, but going to a hospital means doctors can see him in person.

Dr. Rupert Beale, a group leader of the cell biology of infection lab at the Francis Crick Institute for biomedical studies, said doctors would likely be monitoring important vital signs such as oxygen saturations, as well as performing blood tests, assessing Johnsons organ function and possibly performing a CT scan on his chest to assess his lungs.

Foreign Secretary Dominic Raab, who has been designated to take over if Johnson becomes incapacitated, is set to lead the governments coronavirus meeting Monday.

Johnsons fiancee, Carrie Symonds, 32, revealed Saturday that she spent a week in bed with coronavirus symptoms, though she wasnt tested. Symonds, who is pregnant, said she was now on the mend. She has not been staying with the prime minister in Downing St. since his diagnosis.

The government said Sunday that almost 48,000 people have been confirmed to have COVID-19 in the U.K., and 4,934 have died.

Johnson replaced Theresa May as Conservative prime minister in July and won a resounding election victory in December on a promise to complete Britains exit from the European Union. But Brexit, which became official Jan. 31, has been overshadowed by the coronavirus pandemic sweeping the globe.

Johnsons government was slower than those in some European countries to impose restrictions on daily life in response to the pandemic, leading his critics to accuse him of complacency. He imposed an effective nationwide lockdown March 23, but his government remains under huge pressure to boost the countrys number of hospital beds and ventilators and to expand testing for the virus.

London has been the center of the outbreak in the U.K., and politicians and civil servants have been hit hard. Several other members of Johnsons government have also tested positive for the virus, including Health Secretary Matt Hancock and junior Health Minister Nadine Dorries. Both have recovered.

News of Johnsons admission to hospital came an hour after Queen Elizabeth II made a rare televised address to the nation, in which she urged Britons to remain united and resolute in the fight against the virus.

We will succeed and that success will belong to every one of us, the 93-year-old monarch said, drawing parallels to the struggle of World War II.

We should take comfort that while we may have more still to endure, better days will return: we will be with our friends again; we will be with our families again; we will meet again, she said.

Follow AP news coverage of the coronavirus pandemic at http://apnews.com/VirusOutbreak and https://apnews.com/UnderstandingtheOutbreak

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UK Prime Minister Boris Johnson hospitalized with virus - The Republic

Cell Biology

From the meme page to a UC Davis-themed viral TikTok, how students are using social media during the pandemic – The Aggie

Students share their thoughts on memes, mobile apps, websites in light of COVID-19, social distancing

As with any unprecedented event, memes about COVID-19 and online classes are abundant and highly popular. The Facebook group Zoom Memes for Self Quaranteens, formatted in the style of other college meme pages and created on March 11, has over 510,000 members at the present moment and is described as a meme page for college studs stuck doing online courses in closed universities.

On Instagram, users are participating in a variety of challenges that include drawing carrots on their stories and tagging friends, posting ugly pictures with the caption until tomorrow and sharing a list of people who inspire them. According to a Business Insider article, TikTok was approaching 2 billion installs as of March 13 and was the most popular non-gaming app worldwide something the publication attributed to bored users impacted by the virus [] logging daily life under quarantine and social distancing.

Third-year electrical engineering major Gauruv Virk uses Instagram, Twitter, Facebook, Snapchat, Wildfire and YouTube on a daily basis, and he posts to his YouTube channel once a week. Virk said that in a time of crisis such as this, its crucial that social media put out as much accurate and helpful information as possible.

I think it is important that the public is at a place where they can trust the information they receive in order to make informed decisions for themselves and those around them, Virk said via email. Ive also always valued humor and entertainment, and during times like these I think its important for social media to provide as much of it as possible as a way to keep people distracted and at ease.

Virk said the pandemic is currently being addressed all over social media pointing to examples of YouTube videos that depict people in group settings appearing alongside disclaimers stating that these videos were filmed before shelter-in-place took effect.

The influence of meme pages and trends cant be ignored in times like these, Virk said via email. They are the new way of conveying topical information to an incredibly impressionable and media-driven population, and so to dismiss them entirely would be a disservice to anyone that is trying to stay informed in todays world.

TikTok

Second-year cell biology major Mehrab Hussain downloaded TikTok last summer when he was studying abroad.

I downloaded TikTok solely to watch one creator, Hussain said via email. I had seen some of his videos posted on Instagram and really loved him, but refused to download TikTok, as I was going through the phase that everyone initially goes through regarding the app: its stupid, cringe and a waste of time. I eventually caved and downloaded the app, only following the creator who I wanted to see and limiting myself to that. That didnt last long though, as I fell down the rabbithole of downloading TikTok casually or as a joke, then becoming addicted and finding myself scrolling mindlessly for hours on end.

Last month, around the beginning of when the world started to fall apart, Hussain made a Davis-related TikTok that went viral. His TikTok, which references the tornado that touched down in Davis in late September, the WarnMe notice alerting students to a man armed with a machete seen on campus in early March and the ongoing COVID-19 pandemic, was posted on the UC Davis meme page on March 10 and received over 1,000 likes. After that, he saw it go viral on TikTok, receiving more than 270,000 views, 34,000 likes and 200 comments.

We were coming up on finals, COVID-19 was still serious, but not serious enough to [move Spring Quarter online] yet and it was a time of great uncertainty, fear and confusion, Hussain said via email. There were just so many crazy events going on at the time, and during the school year for us Aggies [] that I figured why not do something that would lighten everyones spirits.

Even though the TikTok took a while for Hussain to put together and involved many outfit changes, the idea came to him all at once probably while he was zoning out in one of his classes, he said.

Friends from out-of-state and people he hadnt talked to since middle school reached out to tell Hussain that he was on their For You page a customized page curating specific content for every TikTok user.

To me that was the craziest thing, somehow being everywhere and having all my friends, both local and from other states, and thousands of strangers hype me up and support me, Hussain said via email. My sister in high school even texted me saying that I had been the first video to show up on her For You Page. It boggles my mind how many people it reached, and how many of my own friends and their friends from all over somehow saw me.

Hussain said the most shocking incident was when someone walked up to ask if he was the guy in the TikTok video that she had loved and reposted.

I found out that she was actually in my class, but we did not know each other and she somehow recognized me and remembered seeing my face in class, Hussain said via email. I was in shock after, just about how someone actually recognized me on campus from a video online. To top it all off, she asked me after class if I could take a picture with her! At that point I was just so at a loss for words and shook, to put it simply.

Hussain has noticed changes to TikTok since the outbreak of COVID-19, notably through the content on the app. Not only are there more hashtags and memes, but there are also videos with preventative tips and even a warning about the virus, which his video received. He also shared his thoughts on how COVID-19 and social distancing are impacting creators.

Were confined to our homes and forced to stay inside, obviously for the better, as the only way to slow this virus down is through social distancing, Hussain said. I think in order to entertain themselves, more and more people have given up the preconceived negative notion of TIkTok and downloaded it. Ever since the quarantine, I noticed a lot more smaller creators and videos that had not amassed thousands of likes, which I found really cool since this meant more people were creating content and the app was constantly getting saturated with more and new videos.

Facebook meme pages

There has been quite a lot of activity on the UC Davis Memes for Egghead Teens page on Facebook some, but not all, of which has to do with COVID-19 and related changes to instruction and administration.

Third-year computer science and economics double major Julie Deng and third-year computer science major Jason Lin made the Davis Purity Test out of quarantine boredom and posted it to the meme page on March 28. The website describes it as an unofficial purity test designed to satirize the ideal experience of a student at UC Davis, inspired by the Rice Purity Test and the Berkeley Purity Test.

Everyone was reposting the UC Davis bingo on their Instagram stories, Deng said. So we figured that we wanted to do an extended version of that and just had the Davis Purity Test as the result.

They noted that the test looks similar to the original, as they used the original template accessible on GitHub, made changes to formatting and background and changed the questions, with the help of some friends, to be UC Davis-specific. Deng said she asked a few of her friends for some of the 21 plus questions because she is underage and wanted their input about bars.

It was interesting to see people tag all of their friends, and they thought it was pretty impressive, Lin said. We didnt really put that much time into making it, so it made us feel pretty good.

Another popular meme in the UC Davis meme page, created by fifth-year design and electrical engineering double major Karli Ching, has the text when you realize Canvas is the coronavirus in disguise with a side-by-side comparison emphasizing the similarities between the Canvas logo and the visual representation of the COVID-19 virus. The post received over 1,000 likes.

This was Chings first meme she was reading about COVID-19 and happened to go to Canvas immediately after.

Many of us, including myself, often joke about how Canvas and school are evil, Ching said via email. I saw the Canvas logo and thought it looked like the virus image that I had just seen in the article I read, and decided to make the meme.

Ching thinks that viral memes can help clue people in to significant events, something that Virk and Hussain also mentioned.

Since people have been adhering to social-distancing and shelter-in-place, Ching said meme content relates to these new norms, but the memes themselves dont really change.

I think memes are a humorous way for us to face reality, and I think humor is a way for us to also find relief in stressful situations, Ching said via email.

Written by: Anjini Venugopal features@theaggie.org

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From the meme page to a UC Davis-themed viral TikTok, how students are using social media during the pandemic - The Aggie

Cell Biology

HKU biomedical engineers achieve significant breakthrough in neuroimaging with novel high-speed microscope to capture brain neuroactivities – India…

Our brain contains tens of billions of nerve cells (neurons) which constantly communicate with each other by sending chemical and electrical flashes, each lasting a short one millisecond (0.001 sec). In every millisecond, these billions of swift-flying flashes altogether traveling in a giant star-map in the brain that lights up a tortuous glittering pattern. They are the origins of all body functions and behaviours such as emotions, perceptions, thoughts, actions, and memories; and also brain diseases e.g. alzheimers and parkinsons diseases, in case of abnormalities.

One grand challenge for neuroscience in the 21st century is to capture these complex flickering patterns of neural activities, which is the key to an integrated understanding of the large-scale brain-wide interactions. To capture these swift-flying signals live has been a challenge to neuroscientists and biomedical engineers. It would take a high-speed microscope into the brain, which has not been possible so far.

A research team led by Dr Kevin Tsia, Associate Professor of the Department of Electrical and Electronic Engineering and Programme Director of Bachelor of Engineering in Biomedical Engineering of the University of Hong Kong (HKU); and Professor Ji Na, from the Department of Molecular & Cell Biology, University of California, Berkeley (UC Berkeley) offers a novel solution with their super high-speed microscope two-photon fluorescence microscope, which has successfully recorded the millisecond electrical signals in the neurons of an alert mouse.

The new technique is minimally invasive to the animal being tested compared to the traditional method that require inserting an electrode into the brain tissue. Not only is this less damaging to the neurons but also can pinpoint individual neurons and trace their firing paths, millisecond by millisecond.

The result of this ground-breaking work has recently been published in the academic journal Nature Methods. The project was funded by the National Institute of Health, U.S.

At the heart of the high-speed microscope is an innovative technique called FACED (free-space angular-chirp-enhanced delay imaging) developed by Dr Tsais team earlier (note 1). FACED makes use of a pair of parallel mirrors which generate a shower of laser pulses to create a super-fast sweeping laser beam at least 1,000 times faster than the existing laser-scanning methods.

In the experiment, the microscope projected a beam of sweeping laser over the mouses brain and captured 1,000 to 3,000 full 2D scans of a single mouse brain layer (of the neocortex) every second. To probe the genuine electrical signals that pulse between the neurons, the team inserted a biosensor (protein molecules), developed by Dr Michael Lin of Stanford University, into the neurons of the mouse brain.

These engineered proteins will light up (or fluoresce) whenever there is a voltage signal passes through the neurons. The emitted light is then detected by the microscope and formed into a 2D image that visualises the locations of these voltage changes, said Dr Tsia.

This is really an exciting result as we now can peek into the neuronal activities, that were once obscured and could provide the fundamental clues to understanding brain functions and more importantly brain diseases, he added.

Apart from electrical signals, the team also used the microscope to capture the slow-motion of chemical signals in the mouse brain, such as calcium and glutamate, a neurotransmitter, as deep as one-third of a millimeter from the brains surface.

A notable advantage of this technique is the ability to track the signals that do not trigger the neuron to fire weak neuronal signals (called sub-threshold signals) that are often difficult to capture and detect, which could also happen in many disease condition in the brain, but have yet been studied in detail because of the lack of high-speed technique like the one developed by the team.

Another important feature of the novel technique is that it is minimally invasive. The classical method for recording electrical firing in the brain is to physically embed or implant electrodes in the brain tissue. However, such physical intrusion could cause damage to the neurons, and can only detect fuzzy signals from a couple of neurons.

This is so far a one-of-its-kind technology that could detect millisecond-changing activities of individual neurons in the living brain. So, this is, I would say, the cornerstone of neuroscience research to more accurately decoding brain signals.Dr Tsia said the team would work to advance the capability of the microscope.

We are working to further combine other advanced microscopy techniques to achieve imaging at higher resolution, wider view and deeper into the brain in the neocortex, which is about 1 millimeter. This will allow us to probe deeper into the brain for a better and more comprehensive understanding of the functions of the brain. he added.

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Cell Biology

TGen, Amgen, CeMM, And More: Bio-IT Community Rallies Against COVID-19 – Bio-IT World

April 10, 2020 Coronavirus research, tools and offerings are advancing at a breakneck pace. The SARS-CoV-2 virus is serving as a rallying cry across the bio-IT landscape inspiring creative new solutions, partnerships, and ideas to address the outbreak, treat and prevent the disease it causes, and address the life adjustments of our new normal. Here are some of the free tools, new solutions, and research this week.

Industry News

TheTranslational Genomics Research Institute(TGen),an affiliate of City of Hope,The Pathogen and Microbiome Institute at Northern Arizona Universityand the Ecology and Evolutionary Biology Department at theUniversity of Arizonahave formedthe Arizona COVID-19 Genomics Union totrack the COVID-19 coronavirusby harnessing the power of state-of-the-art technology and "big data" analysis. Scientists will sequence samples from COVID-19 patients to analyze the virus' genetic codes, track its different strains, show where each sample originates from, where it may have been transmitted andpossiblyuncovercritical information for diagnostics, anti-viral drug targets and vaccine development.Press release.

AmgenandAdaptive Biotechnologiesarecombiningexpertise to discover and develop fully human neutralizing antibodies targeting SARS-CoV-2 to potentially prevent or treat COVID-19. The mutually exclusive collaboration brings togetherAdaptive'sproprietary immune medicine platform for the identification of virus-neutralizing antibodies with Amgen's expertise in immunology and novel antibody therapy development.Neutralizing antibodies defend healthy cells by interfering with the biological function of an invading virus. These antibodies may be used therapeutically to treat someone currently fighting the disease and can be given to people who have heightened risk of exposure to SARS-CoV-2, such as healthcare workers.Press release.

Researchers from theCenterForMolecular MedicineOfTheAustrian AcademyOfSciences (CeMM) have released SARS-CoV-2 genomesfrom Austrian patients. Initial sequence analysis of the 29,900 nucleotide-long SARS-CoV-2 genomes from Austria revealed on average 6 mutations different to the reference genome isolated in Wuhan. The observed number of mutations is in line with other recently reported SARS-CoV-2 genomes. Most of the observed mutations lead to changes in viral proteins, providing evidence for positive selection pressure and evolution within the human population. Assessing the actual impact of these mutations for the virus life cycle and its interactions with both the host and the immune system will be within the scope of future investigations.Press release.

IRB Barcelona's Structural Bioinformatics and Network Biology Laboratoryhas joined forces with Amazon to develop the Chemical Checker, a computational tool that would help process academic literature on COVID-19. Using artificial intelligence, this tool will "read" articles and extract all relevant information related to the molecules and treatments studied. Through a limited review of the most relevant scientific literature, researchers at IRB Barcelona have so far identified more than 150 compounds that are potentially active against COVID-19. Results are already available athttps://sbnb.irbbarcelona.org/covid19/. The experience Amazon has with text-mining, machine learning and natural language understanding has allowed the automatic analysis of scientific articles to be incorporated into the Chemical Checker at a fast pace.Chemical Checker and results.

Flinders Universityresearchers working withOracle Cloudtechnology and vaccine technology developed by local companyVaxine,are testing avaccine candidate against the SARS-CoV-2coronavirus responsible for the COVID-19 pandemic.Oracle wastapped for technical collaboration, access to an expanded research community, and cloud infrastructure that helped enable the rapid design of the novel COVID-19 vaccine candidate.The Australian teamused computer models of the spike protein and its human receptor, ACE2, to identify how the virus was infecting human cells, and then were able to design a vaccine to block this process.Press release.

Through the end of 2020,Sandia National Laboratoriesisofferingany U.S. personnonexclusive, fast-tracklicensesfree of chargetomore than 1,000 patentedtechnologies. Thegoal of theRapid Technology Deployment Programisto enablelicensees to invest their full resources into combating theCOVID-19pandemic and its economic effects.

Japanis putting itsflagshipsupercomputerFugakuto work in combatting the pandemicby giving priority toCOVID-relatedresearch selected by the Japanese Ministry of Education, Culture, Sports, Science and Technology. Installation of the new supercomputer began in December and isnt scheduled to go into full-fledged open useuntil2021, but someof the nodesare going intotrial useas of April1.Press release.

Latest from the Literature

A collaborativein vitrostudy led byMonash University's Biomedicine Discovery Institute(BDI)in Melbourne, Australia, with thePeter Doherty Institute of Infection and Immunity(Doherty Institute), has shown that ananti-parasitic drugalready available around the world kills the virus within 48 hours.The drug, Ivermectin, stopped the SARS-CoV-2 virus growing in cell culture within 48 hours.Ivermectin is an FDA-approved anti-parasitic drug that has also been shown to be effective in vitro against a broad range of viruses including HIV, Dengue, Influenza and Zika virus.The study was published online inAntiviral Research.DOI:10.1016/j.antiviral.2020.104787

A multidisciplinary team of scientists atThe University of Texas Medical Branch(UTMB)at Galveston have developedareverse genetic systemthatallows researchers tomake SARS-CoV-2 in the lab and manipulate it in a petri dishspeeding thedevelopmentandevaluation ofvaccines, diagnose infected patients and exploreevolution ofthe virus.The system has been used tolabel the virussoinfectedcellsturn green,creatingahigh-throughputtestsignificantly reducing the time it takes to evaluate and bring candidate vaccines to market.UTMBis making thetechnology available to academia and industry researchers working to quickly developCOVID-19countermeasures. On-campus scientistswill nowdeploy the technology forblood-based diagnostictesting.Thestudy willbe publishedinCell Host & Microbe. DOI:10.1016/j.chom.2020.04.004

Thereceptor for SARS-CoV-2 is abundantly expressed in certain progenitor cellsthatnormally develop into respiratory tract cells, according to scientistsattheBerlin Institute of Health,Charit-UniversittsmedizinBerlinand the Thorax Clinic at Heidelberg University Hospital. The discovery, whichwillbe published inThe EMBO Journal (DOI:10.15252/embj.20105114),emerged from anexamination ofsamples from non-virus-infected patientsusing used single-cell sequencing technology.An additional, preliminary finding was that receptor density on the cells increased with age andwasgenerally higher in men than in women.Dellwas responsible for the reduced processing time needed to sequence 60,000 single cells.

AUniversity of Ottawabiology professor believesstray dogsspecifically dog intestinesmaybe theorigin of the current SARS-CoV-2 pandemic.Hisstudy involved examining full-lengthbetacoronavirusgenomes that have been deposited into GenBank, a National Institutes of Health genetic sequence database.Evidence willbepublishedinMolecular Biology and Evolution(http://dx.doi.org/10.1093/molbev/msaa094). While study findings are of vital interest in the current world health crisis, theymore broadly suggest that viralevolution can be revealed bylooking at theinteraction of host defenses with viral genomes.

Researchersin the UK and GermanyreportinPNASa phylogenic network of 160SARS-CoV-2genomes, revealing three major typesof variantsone found predominantly within East Asia and the other two in Europeans and Americans.The networkreconstructsdocumented routes of infectionand might be used to trace unknown infection sourcesthatcan then be quarantined toprevent recurrent spreadof the disease worldwide.DOI:10.1073/pnas.2004999117

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TGen, Amgen, CeMM, And More: Bio-IT Community Rallies Against COVID-19 - Bio-IT World

Cell Biology

Column: Biology basics: What is a virus, bacteria, fungus? And how can we kill them? – The Morning Sun

With the coronavirus on everyones mind, lets go back to some basics. Like what is a virus and how do we get rid of it? Modern medicine seems to cure most anything, so why is it so hard to destroy the coronavirus?

There are three major pathogens (biological structures that can make humans ill). They are bacteria (bacterium), fungi (fungus) and viruses (virus). Each one is unique in its structure and complexity. Therefore, the way to destroy each of them is also unique.

We are exposed to thousands, if not millions, of unique pathogens. Our immune system must learn how to destroy each and every one. When we are born, we have almost no immune system; we are incredibly vulnerable to infection and sickness. We must build up our immune system with antibodies. Antibodies are how the immune system can identify, tag, and destroy the pathogens making a person sick. The only way an immune system can build up antibodies is to be exposed to a pathogen and learn how to identify, tag, and destroy the pathogen. The only shortcut to this is when a mother can pass some antibodies to a nursing infant through her breast milk. (This is only one of the many reasons why a newborn should be breast fed.)

However, once our immune systems have the antibodies needed to identify, tag, and destroy a specific pathogen, it will remember that pathogen. So, the next time you are exposed to it, your immune system will produce the antibodies to destroy the pathogen much quicker, ideally even before you feel sick.

Sometimes our immune systems cannot do it on its own, that is where medicine is required. Remember, there are bacteria, fungal and viral pathogens.

First, fungi tend to be external organisms that live on surfaces. Mold, mushrooms, and mildew are some classic examples and good to use as a reference. They grow in dark, moist places on decaying matter. The hypha or roots burrow into the organic matter to extract the nutrients it needs for life. Athletes foot, jock itch and yeast infections are all common pathogens many of us have suffered. Although, internally fungi are lethal, they are rare. Most external fungi can be destroyed with an anti-fungal cream or pill. Fungi tend to be on the low side of complexity and relatively easy to kill.

Bacterial pathogens are individual living organisms. They are the germs that we think of swimming around under a microscope. There are millions of varieties of them. They live on their own, on surfaces within the air, in foods and water. Many ear, throat, and sinus infections are bacterial. Fortunately, our immune system is pretty good at identifying these foreign organisms living within our bodies and can destroy them on its own. And if it cannot, a doctor can prescribe an antibiotic (penicillin) to finish the job.

On the other hand, viruses are non-living, they are DNA pirates. They cannot live or reproduce on their own. Think of a virus as a blob of grease or oil with a single strand of DNA within it. No nucleus, no organelles, just a microscopic ball of fat with a code to cause some biological mutiny.

Viruses require a host cell for reproduction. The virus does this by taking over a host cell and forcing the cell to reproduce the virus and its fatty shell, much like a pirate hijacking a ship for its own purposes. Unfortunately, the cell will no longer be able to perform the life-sustaining job it was intended to be doing; hence you feel sick. The host cell will continue to perform the pirates task, reproduce the virus, until it destroys itself. Then, liberating more DNA pirates to repeat the process.

The fact that the virus lives inside the cell makes it hard for the immune system to identify the pathogen, let alone destroy it. The only way to destroy the virus is to destroy the cell itself. The pirate will never leave the ship, the ship must be destroyed to kill the pirate.

This is what our immune systems does anti-bodies identify, tag, and destroy the living cells that have the virus within them. This explains our symptoms which can range from minor aches and pains to lethal tissue and organ damage. Your immune system is literally destroying your own cells.

Fortunately, we have billions of cells and our immune system can be very targeted once the anti-bodies have figure out which cells have been pirated by the virus. White blood cells can then effectively destroy only the pirated cells and recovering will begin.

A major problem with the coronavirus in humans is our immune systems have a hard time identifying which cells have been pirated by the virus and which cells are still healthy. Human immune systems seem to be over-reacting and destroying all the surrounding cells. Since the virus is often found in the lungs, heart, and kidneys these are the organs that seem to be suffering the most.

So how do we destroy the coronavirus? They only thing that can destroy a virus is our own immune system. The medical field has had little success in developing anti-viral medications. We can only support our immune system to learn quicker, to produce the antibodies needed and then the immune system can become much more targeted.

Vaccines do this by providing a weakend version for the immune system to learn from. Anti-body therapy takes the anti-bodies from one immune system that has already learned how to identify the virus and directly gives it to an un-learned immune system.

Unfortunately, we do not have any solutions yet! So, the best way to be healthy is to not get sick in the first place. Stay away from the pirates! You all know what to do, washing your hand, social distance, etc. Be safe.

Andrew J. Frisch is a teacher at Farwell High School.

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Column: Biology basics: What is a virus, bacteria, fungus? And how can we kill them? - The Morning Sun

Cell Biology

HKU Biomedical Engineering develops novel 3D imaging technology to make fluorescence microscopy more efficient and push the boundaries of living cells…

Scientists have been using fluorescence microscopy to study the inner workings of biological cells and organisms for decades. However, many of these platforms are often too slow to follow the biological action in 3D; and too damaging to the living biological specimens with strong light illumination.

To address these challenges, a research team led by Dr Kevin Tsia, Associate Professor of the Department of Electrical and Electronic Engineering and Programme Director of Bachelor of Engineering in Biomedical Engineering of the University of Hong Kong (HKU), developed a new optical imaging technology Coded Light-sheet Array Microscopy (CLAM) which can perform 3D imaging at high speed, and is power efficient and gentle to preserve the living specimens during scanning at a level that is not achieved by existing technologies.

This advanced imaging technology was recently published in Light: Science & Applications. An US patent application has been filed for the innovation.

CLAM allows 3D fluorescence imaging at high frame rate comparable to state-of-the-art technology (~10s volumes per second). More importantly, it is much more power efficient, being over 1,000 times gentler than the standard 3D microscopes widely used in scientific laboratories, which greatly reduces the damage done to living specimens during scanning, explained Dr Tsia.

Existing 3D biological microscopy platforms are slow because the entire volume of the specimen has to be sequentially scanned and imaged point-by-point, line-by-line or plane-by-plane. In these platforms, a single 3D snapshot requires repeated illumination on the specimen. The specimens are often illuminated for thousands to million times more intense than the sunlight. It is likely to damage the specimen itself, thus is not favorable for long-term biological imaging for diverse applications like anatomical science, developmental biology and neuroscience.

Moreover, these platforms often quickly exhaust the limited fluorescence budget a fundamental constraint that fluorescent light can only be generated upon illumination for a limited period before it permanently fades out in a process called photo-bleaching, which sets a limit to how many image acquisitions can be performed on a sample.

Repeated illumination on the specimen not only accelerates photo-bleaching, but also generates excessive fluorescence light that does not eventually form the final image. Hence, the fluorescence budget is largely wasted in these imaging platforms, Dr Tsia added.

The heart of CLAM is transforming a single laser beam into a high-density array of light-sheets with the use of a pair of parallel mirrors, to spread over a large area of the specimen as fluorescence excitation.

The image within the entire 3D volume is captured simultaneously (i.e. parallelized), without the need to scan the specimen point-by-point or line-by-line or plane-by-plane as required by other techniques. Such 3D parallelization in CLAM leads to a very gentle and efficient 3D fluorescence imaging without sacrificing sensitivity and speed, as pointed out by Dr Yuxuan Ren, a postdoctoral researcher of the work. CLAM also outperforms the common 3D fluorescence imaging methods in reducing the effect of photo-bleaching.

To preserve the image resolution and quality in CLAM, the team turned to Code Division Multiplexing (CDM), an image encoding technique which is widely used in telecommunication for sending multiple signals simultaneously.

This encoding technique allows us to use a 2D image sensor to capture and digitally reconstruct all image stacks in 3D simultaneously. CDM has never been used in 3D imaging before. We adopted the technology, which became a success, explained by Dr Queenie Lai, another postdoctoral researcher who developed the system.

As a proof-of-concept demonstration, the team applied CLAM to capture 3D videos of fast microparticle flow in a microfluidic chip at a volume rate of over 10 volumes per second comparable to state-of-the-art technology.

CLAM has no fundamental limitation in imaging speed. The only constraint is from the speed of the detector employed in the system, i.e. the camera for taking snapshots. As high-speed camera technology continually advances, CLAM can always challenge its limit to attain an even higher speed in scanning, highlighted by Dr Jianglai Wu, the postdoctoral research who initiated the work.

The team has taken a step further to combine CLAM with HKU LKS Faculty of Medicines newly developed tissue clearing technology to perform 3D visualization of mouse glomeruli and intestine blood vasculature in high frame-rate.

We anticipate that this combined technique can be extended to large-scale 3D histopathological investigation of archival biological samples, like mapping the cellular organization in brain for neuroscience research. Dr Tsia said.

Since CLAM imaging is significantly gentler than all other methods, it uniquely favours long term and continuous surveillance of biological specimen in their living form. This could potentially impact our fundamental understanding in many aspects of cell biology, e.g. to continuously track how an animal embryo develops into its adult form; to monitor in real-time how the cells/organisms get infected by bacteria or viruses; to see how the cancer cells are killed by drugs, and other challenging tasks unachievable by existing technologies today, Dr Tsia added.

CLAM can be adapted to many current microscope systems with minimal hardware or software modification. Taking advantage of this, the team is planning to further upgrade the current CLAM system for research in cell biology, animal and plant developmental biology.

This project is an interdisciplinary collaboration between HKU Faculty of Engineering and LKS Faculty of Medicine. It was funded by HKSAR Research Grants Council, Innovation and Technology Support Program, the University Development Funds of the University of Hong Kong and the Natural Science Foundation of China.

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HKU Biomedical Engineering develops novel 3D imaging technology to make fluorescence microscopy more efficient and push the boundaries of living cells...

Cell Biology

Princeton awards over half-a-million dollars in funding for rapid, novel and actionable COVID-19 research projects – Princeton University

With the aim of accelerating solutions to the challenges of the COVID-19 pandemic, Princeton has awarded University funding for seven new faculty-led research initiatives with strong potential for impact.

The funding enables faculty and their teams to address crucial questions in biomedical, health-related and fundamental science, as well as policy, social and economic topics. Projects will receive funding of up to $100,000.

The projects include research on asymptomatic transmission, immunity following infection, vaccines, new treatments, contact tracing, economic implications of social distancing, challenges unique to urban environments, and strategies for reducing pandemic-associated domestic violence.

The University's support for new research against COVID-19 was spurred by a groundswell of requests from faculty, said Dean for Research Pablo Debenedetti, whose office coordinated the application process and the review of the proposals.

"Many members of the Princeton faculty have reached out with requests for opportunities to use their knowledge, ideas and skills to assist in combating the COVID-19 pandemic," said Debenedetti, the Class of 1950 Professor in Engineering and Applied Science and a professor of chemical and biological engineering. "The quality of the proposals received is a testament to the creativity of our faculty and to their dedication to the common good in this challenging time."

The seven projects were chosen following a competitive application process with proposals evaluated by a committee of peers. The funding supports the creation of new knowledge rather than production of materials or equipment for clinical purposes, which is being addressed by Princeton's COVID-19 Response Special Activities and Resources Group. Consideration was given to the unique needs facing the state of New Jersey, as well as the broader needs arising from the pandemic.

Reflecting the immediacy of the situation, researchers must report on their progress after three months, at which time only projects that have made appreciable progress will be allowed to continue.

Some projects will require access to laboratories and other campus spaces which are restricted due to New Jersey's stay-at-home order. These new projects will join a small number of campus-based projects deemed essential following earlier review by the Office of the Dean for Research.

The selected projects are:

Monitoring SARS-CoV-2 in Princeton: Quantifying viral transmission and building an understanding of immunity

Andrea Graham, professor of ecology and evolutionary biology

Bryan Grenfell, the Kathryn Briger and Sarah Fenton Professor of Ecology and Evolutionary Biology and Public Affairs, Woodrow Wilson School

C. Jessica Metcalf, assistant professor of ecology and evolutionary biology and public affairs, Woodrow Wilson School

Julien Ayroles, assistant professor of ecology and evolutionary biology and the Lewis-Sigler Institute for Integrative Genomics

Researchers will combine viral testing for active infections with evaluations of the immune response of individuals in the community of Princeton to provide much needed resolution on the question of asymptomatic transmission of SARS-CoV-2, the virus responsible for COVID-19. The project will also provide a foundation from which to probe the development of an immune response to the virus, with the potential to inform our understanding of what the immune response means in terms of protection from infection.

Development of critical reagents to accelerate drug and vaccine development against SARS-CoV-2

Alexander Ploss, associate professor of molecular biology

The team aims to develop a version of SARS-CoV-2 that is less dangerous to laboratory workers and that can be safely handled under less stringent safety controls, thus broadening the ability of more researchers to study the virus. The researchers will also evaluate the therapeutic efficacy of certain FDA-approved compounds that have been shown to interfere with the replication of numerous viruses, as well as test a potential vaccine approach. They also will work to establish a humanized mouse model that can be used for preclinical testing of drug and vaccine candidates.

Fine-grained, privacy-respecting contact traceback for COVID-19 epidemiology

Kyle Jamieson, associate professor of computer science

Leveraging advances in mobile tracking, this project aims to automate the identification and traceback of recent significant risk contacts of a confirmed COVID-19 case. Instead of relying on GPS, which doesnt work well indoors and in many urban settings, the new approach employs more granular information from the cellular networks control channel to determine whether and for how long people spend time near a confirmed positive case.

Proposal for identifying small molecules targeting SARS-CoV-2 spike binding to human ACE2 cell receptor

Cliff Brangwynne, professor of chemical and biological engineering

Researchers will search for molecules that disrupt the cycle of infection by blocking the interaction between the virus's spike proteins and theACE2 receptors on human cells. The team will screen thousands of known bioactive compounds, including ones with prior FDA approval for other indications that could be rapidly deployed. Upon identifying promising compounds, the team will work with partner labs to move these candidates toward clinical testing.

Evaluating the economic implications and costs of COVID-19 social distancing policies

Natalie Bachas, assistant professor of economics

Arlene Wong, assistant professor of economics

Drawing on the collection of large datasets, the researchers will conduct an analysis to help inform the level of social distancing that balances health outcomes and economic consequences. These estimates will help guide the policy debate on how to both flatten the infection curve and the economic cost curve. The researchers will also evaluate the effectiveness of the payouts to households and provide key estimates on the economic spillovers of closures from essential and non-essential businesses.

Manual of urban distance: Strategies for reconfiguring the city

Paul Lewis, professor of architecture

Guy Nordenson, professor of architecture

Physical distancing and urban density are diametrically opposed, so new strategies are needed that rework the design of cities for a beneficial urban future. This project addresses the near-term problems of urban distancing during peak infection, as well asafter restrictions are eased but the population is still at risk of a rebound. The second phase of the project will look at longer term and more permanent strategies that consider possible future resurgence of COVID-19 as well as future pandemics.

Macroeconomic shocks and domestic violence: Evidence from COVID-19

Maria Micaela Sviatschi, assistant professor of economics and public affairs, Woodrow Wilson School

With unemployment on the rise and large numbers of people working from home, the potential for financial and emotional stress could potentially lead to increased domestic violence. Thisteam will evaluate COVID-19's impact on domestic violence and aims to test two interventions that are likely to determine pathways to aid victims during a pandemic: one that provides labor market opportunities for women and a second that provides information on how to identify and respond in domestic violence cases.

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Princeton awards over half-a-million dollars in funding for rapid, novel and actionable COVID-19 research projects - Princeton University

Cell Biology

CYTOVIA Therapeutics and MACROMOLTEK to Develop Dual-Acting Natural Killer Immunotherapy Against SARS CoV2 (COVID-19) – GlobeNewswire

NEW YORK and AUSTIN, Texas, April 07, 2020 (GLOBE NEWSWIRE) -- Cytovia Therapeutics (Cytovia), an emerging biopharmaceutical company developing Natural Killer (NK) immunotherapies for cancer and infectious diseases, announced today that it is expanding its programs to help urgently address the current SAR CoV2 (COVID-19) crisis.

Natural Killer cells are a first line of defense not only against tumor cells but also against severe acute infectious diseases. Using a bi-functional approach has the potential to minimize virus escape from the immune response thereby inhibiting the intensification of the inflammation leading to Acute Respiratory Syndrome (ARS). The activation of NK cells through the NKp46 receptor aims to destroy the virus-infected cells while the other arm can either block the entry of the virus into epithelial cells or neutralize circulating viruses.

Dr Daniel Teper, co-founder, Chairman and CEO of Cytovia said: Our goal is to bring the best candidate to clinical trials by the end of the year 2020 and make it available to patients in 2021. As we become more prepared for potential next waves of the pandemic, physicians will need therapeutic options to strengthen the immune response and prevent rapid worsening of the disease. We expect that our novel approach might also be applied in the future to other severe acute infectious diseases, an area that still has significant unmet medical needs. Partnering with Macromoltek will fast-track this process.

Dr Monica Berrondo, co-founder and CEO of Macromoltek added: Our computational approach to antibody design allows to fast track the development of optimal therapeutic candidates in weeks rather than months. In the fight against SARS CoV2, time is of the essence. We are delighted to be part of a multi-disciplinary team passionate about winning the race against the virus with novel therapeutic solutions.

Cytovia will lead a highly coordinated team of scientific collaborators in order to achieve aggressive timelines for its COVID-19 therapeutic program. Cytovia will leverage its own proprietary bi-functional technology, developed by co-founder Dr Kadouche, NK activating antibodies licensed last month from Yissum, the technology transfer company of the Hebrew University of Jerusalem, and novel antibodies neutralizing or blocking SARS CoV2, designed by Macromoltek, a computational antibody discovery company. The selected bi-functional antibodies will further benefit from the Fast to Clinic approach implemented by STC Biologics, a Boston, MA based antibody development and manufacturing company.

About Cytovia TherapeuticsCytovia aims to accelerate patient access to transformational immunotherapies, addressing several of the most challenging unmet medical needs in cancer and severe acute infectious diseases. Cytovia focuses on Natural Killer (NK) cell biology and applies precision medicine tools to develop the right therapy for the right patient at the right stage of the disease. Cytovia has secured access to multiple advanced technologies, including an induced pluripotent stem cell (iPSC) platform for NK cell therapy, gene editing of Chimeric Antigen Receptors (CAR) to enhance targeting of NK cells, and NK engager multi-functional antibodies. Cytovia partners with the University of California San Francisco (UCSF), the New York Stem Cell Foundation (NYSCF) and the Hebrew University of Jerusalem. Learn more at http://www.cytoviatx.com.

About MacromoltekMacromoltek, a computationalde novodrug design company, rapidly producesaccurate and credible antibody designs. They have built a proprietary platform that enables design against difficult targets inaccessible by traditional methods. A Y Combinator cohort company, they are already designing antibodies for several large biopharmas and smaller biotechs. https://www.macromoltek.com

Media and Investor Contacts

Cytovia TherapeuticsSophie Badr(Media)sophiebadre21@gmail.com929.317.1565

Anna Baran Djokovic (Investors)Anna@cytoviatx.com

MacromoltekLisa Hendricksonlhendrickson@sparkcity.co917.912.9424

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CYTOVIA Therapeutics and MACROMOLTEK to Develop Dual-Acting Natural Killer Immunotherapy Against SARS CoV2 (COVID-19) - GlobeNewswire

Cell Biology

Novel research explores interaction between engineered gene circuits and biological host cells – News-Medical.net

Reviewed by Emily Henderson, B.Sc.Apr 7 2020

Recent discoveries by two research teams in the Ira A. Fulton Schools of Engineering at Arizona State University are advancing the field of synthetic biology.

Assistant Professor Xiaojun Tian and Associate Professor Xiao Wang conducted a year-long collaboration with their laboratory groups in the School of Biological and Health Systems Engineering, one of the six Fulton Schools. Results from their novel research into ways that engineered gene circuits interact with biological host cells have been published this week in the scientific journal Nature Chemical Biology.

Synthetic biology applies engineering methods to design new biological networks or redesign aspects of existing biological systems. It is a rapidly emerging field of study, and many significant advances have been made during the past 20 years.

Early work included creating synthetic gene circuits and placing them within natural host cells.

But the concept of a circuit here is an abstract one. Imagine a sequence of genetic segments in which the first one encodes or produces a particular protein. That protein, in turn, can either activate or inhibit the expression or protein production from another segment in the genetic sequence. If you keep expanding this idea, you can imagine it's like a network."

Xiao Wang, Associate Professor,Ira A. Fulton Schools of Engineering at Arizona State University

It is this chain of influence or inducement that is functioning as a circuit, rather than the physical connections within the genetic sequence. However, previous research has focused on just the behaviors of engineered genetic circuits themselves, with little attention to the background or context represented by host cells.

"It is hard to predict how these interactions affect the functions of the engineered genetic circuits," Tian says, "not to mention how to control them and make the circuits operate as desired within complicated, real-life environments."

Indeed, these synthetic gene circuits generally work only in a laboratory environment, not in more lifelike conditions. And this limitation greatly inhibits the application of engineered gene circuits in clinical settings.

Seeking to advance the field in that practical direction, the new research by Tian and Wang explored the relationship between the synthetic gene circuits and their host cells. Specifically, they examined the impact of "memory" circuits implanted within host cells, and the influence of gene circuit "topologies," or the architecture of interconnections among circuit components, in relation to host cell growth.

In the context of this work, the idea of memory relates to the continuation of influence or inducement within an engineered gene circuit even with the absence of a stimulus.

"Think about a light switch in your house," Wang says. "The light stays on even when you remove your finger from the switch. We refer to that persistent state as memory."

Tian and Wang's new research revealed that memory circuit topologies are significantly influenced by host cell behavior.

"We verified that influences are exchanged between the gene circuit and the host cell," Tian says. "That is, the circuit impacts the host cell, which in return has an impact on the circuit. It's like a loop.

"But we also demonstrated that the impact on a circuit's functionality is dependent on its topology," he says. "So, one circuit topology shows better performance than others within a dynamic host environment."

Their discovery relating circuit topology to a host cell's impact on circuit function is a first in the field of synthetic biology, and it expands meaningful scientific understanding of these complex interactions.

"It paves the way for building robust, engineered gene circuits," Tian says. "These could one day enhance interventions against the metastasis of cancer, for example, by slowing the ability of cancer cells to translate their development."

Progressing from the research that Tian and Wang have published includes examining the impact of adding additional synthetic gene circuits or modules into host cells, which substantially elevates the level of complexity as modules compete for resources within the cellular system.

Wang says that the School of Biological and Health Systems Engineering within the Fulton Schools is particularly well-placed for discoveries in synthetic biology.

"We have a critical mass of dedicated people who are strategically invested in advancing this area of research for the long term," he says. "So, we are seeking to be a leader in this field."

Source:

Journal reference:

Zhang, R., et al. (2020) Topology-dependent interference of synthetic gene circuit function by growth feedback. Nature Chemical Biology. doi.org/10.1038/s41589-020-0509-x.

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Novel research explores interaction between engineered gene circuits and biological host cells - News-Medical.net