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Genetics

Fulgent Genetics Announces Increase to Full Year 2020 Guidance to $300 million – Yahoo Finance

TEMPLE CITY, Calif., Nov. 23, 2020 (GLOBE NEWSWIRE) -- Fulgent Genetics, Inc. (NASDAQ: FLGT) (Fulgent Genetics or the company), a technology company providing comprehensive testing solutions through its scalable technology platform, today announced that it has updated its revenue guidance for the full year 2020 due to accelerating demand for its COVID-19 testing solutions.

The company now expects to generate at least $300 million in revenue for the full year 2020, an increase of 28% compared to previous guidance of $235 million. This updated guidance represents estimated year-over-year revenue growth of more than 800%.

Since our Q3 earnings call on November 9th, we have seen accelerating demand for our COVID-19 tests and are raising our full year revenue guidance to reflect this significant increase, said Paul Kim, Chief Financial Officer of Fulgent Genetics. As COVID-19 cases continue to rise across the country, we expect to see increasing demand for testing through the balance of the year. We believe we remain well positioned to meet this demand with our ample resources and capacity to run more than 60,000 tests per day.

About Fulgent Genetics

Fulgent Genetics proprietary technology platform has created a broad, flexible test menu and the ability to continually expand and improve its proprietary genetic reference library while maintaining accessible pricing, high accuracy and competitive turnaround times. Combining next generation sequencing (NGS) with its technology platform, the company performs full-gene sequencing with deletion/duplication analysis in an array of panels that can be tailored to meet specific customer needs. In 2019, the company launched its first patient-initiated product, Picture Genetics, a new line of at-home screening tests that combines the companys advanced NGS solutions with actionable results and genetic counseling options for individuals. Since March 2020, the company has commercially launched several tests for the detection of SARS-CoV-2, the virus that causes the novel coronavirus (COVID-19), including NGS and reverse transcription polymerase chain reaction (RT-PCR) - based tests. The company has received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) for the RT-PCR-based tests for the detection of SARS-CoV-2 using upper respiratory specimens (nasal, nasopharyngeal, and oropharyngeal swabs) and for the at-home testing service through Picture Genetics. A cornerstone of the companys business is its ability to provide expansive options and flexibility for all clients unique testing needs through a comprehensive technology offering including cloud computing, pipeline services, record management, web portal services, clinical workflow, sequencing as a service and automated laboratory services.

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Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Examples of forward-looking statements in this press release include statements about, among other things: anticipated future revenue and guidance; evaluations and judgements regarding demand for the companys testing services, including its COVID-19 testing services, evaluations and judgements regarding the companys resources and its ability to meet any increasing demand for testing services and statements regarding the companys ability to continue to grow its business.

Forward-looking statements are statements other than historical facts and relate to future events or circumstances or the companys future performance, and they are based on managements current assumptions, expectations and beliefs concerning future developments and their potential effect on the companys business. These forward-looking statements are subject to a number of risks and uncertainties, which may cause the forward-looking events and circumstances described in this press release to not occur, and actual results to differ materially and adversely from those described in or implied by the forward-looking statements. These risks and uncertainties include, among others: the ongoing impacts of the COVID-19 pandemic, including the preventive public health measures that may continue to impact demand for its tests and the pandemics effects on the global supply chain; the market potential for, and the rate and degree of market adoption of, the companys tests, including its newly-developed tests for COVID-19 and genetic testing generally; the companys ability to capture a sizable share of the developing market for genetic and COVID-19 testing and to compete successfully in these markets, including its ability to continue to develop new tests that are attractive to its various customer markets, its ability to maintain turnaround times and otherwise keep pace with rapidly changing technology; the companys ability to maintain the low internal costs of its business model, particularly as the company makes investments across its business; the companys ability to maintain an acceptable margin on sales of its tests, particularly in light of increasing competitive pressures and other factors that may continue to reduce the companys sale prices for and margins on its tests; risks related to volatility in the companys results, which can fluctuate significantly from period to period; risks associated with the composition of the companys customer base, which can fluctuate from period to period and can be comprised of a small number of customers that account for a significant portion of the companys revenue; the companys ability to grow and diversify its customer base and increase demand from existing and new customers; the companys investments in its infrastructure, including its sales organization and operational capabilities, and the extent to which these investments impact the companys business and performance and enable it to manage any growth it may experience in future periods; the companys level of success in obtaining coverage and adequate reimbursement and collectability levels from third-party payors for its tests; the companys level of success in establishing and obtaining the intended benefits from partnerships, joint ventures or other relationships; the companys compliance with the various evolving and complex laws and regulations applicable to its business and its industry; risks associated with the companys international operations; the companys ability to protect its proprietary technology platform; and general industry, economic, political and market conditions. As a result of these risks and uncertainties, forward-looking statements should not be relied on or viewed as predictions of future events.

The forward-looking statements made in this press release speak only as of the date of this press release, and the company assumes no obligation to update publicly any such forward-looking statements to reflect actual results or to changes in expectations, except as otherwise required by law.

The companys reports filed with the U.S. Securities and Exchange Commission (SEC), including its annual report on Form 10-K for the year ended December 31, 2019 filed with the SEC on March 13, 2020 and the other reports it files from time to time, including subsequently filed quarterly and current reports, are made available on the companys website upon their filing with the SEC. These reports contain more information about the company, its business and the risks affecting its business, as well as its results of operations for the periods covered by the financial results included in this press release.

Investor Relations Contacts:The Blueshirt GroupNicole Borsje, 415-217-2633; nicole@blueshirtgroup.com

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Fulgent Genetics Announces Increase to Full Year 2020 Guidance to $300 million - Yahoo Finance

Genetics

Caveats in Genetic Testing: Reporting in the Media – The Great Courses Daily News

By Roy Benaroch, M.D., Emory UniversityPersonal genetic testing is now quite common, but consumers should know about the drawbacks. (Image: Dusan Petkovic/Shutterstock)Are the Example Cases Relevant?

In the October 2017, The New York Times, published an article headlined Personal Genetic Testing is Here. Do We Need It? The tone of the article was set by the subheading: Jody Christ, in her home in Elysberg, PA, says genetic testing saved her life, though experts warn such tests require caution.

This article begins with a personal story, in this case, of a 62-year-old Jody Christ who struggled unsuccessfully for years to control her high cholesterol.

A genetic test revealed she had familial hypercholesterolemia, which put her at high risk for atherosclerotic heart disease, and she underwent a triple-bypass heart surgery. The article quotes Ms. Christ, If I had not taken that test I might be dead by now. Thats a dramatic and unequivocal endorsement of this kind of genetic test.

But this startling example isnt a realistic example of the kind of genetic testing that the rest of this article talks about. Ms. Christ had intractably high cholesterol and testing revealed a definite, causal diagnosis. She needed to have been tested for arterial blockages anyway, even without the genetic test.

This is a transcript from the video series The Skeptics Guide to Health, Medicine, and the Media. Watch it now, on The Great Courses Plus.

The remainder of the article discusses testing on asymptomatic people, or people who dont experience any health problems. And that kind of testing is very different.

Continuing from theTimesarticle:

Experts [] also warn that some consumers may be led astray by genetic findings that are overblown or irrelevant. The Centers for Disease Control and Prevention, for example, takes a cautious approach to personal genomics tests, telling consumers on its website to think before they spit and that evidence on the ability of genetic information to change health behavior has been lacking.

But that cautious sentiment is followed by a paragraph about a company offering testing for genetic variants linked to several kinds of cancer, or another test for heart problems. A medical officer at one of these companies says: This is really for people who dont have any reason to think that theyre at particular riskbut the problem is you really dont know unless you do the genetic test.

Some services, according to the article, claim to predict how well youll respond to different medications or even to different kinds of exercises, or which foods you should eat, or even which types of wine you might prefer.

So, the tests range from things that have at least some scientific support to claims that are just silly. Quoting a professor of genetics, the article says, Theres this mixture of some that have real solid footing and then some that have zero footing.

TheTimesarticle, though beginning with a personal endorsement, did at least superficially present a caveat, by covering the shortcomings inherent in the interpretation of these tests.

Learn more abouthow to better understand and evaluatemedical data.

A 2017Huffington Postarticle focused on a different caveat that ought to be considered before testing. Titled What to Consider Before Taking a 23andMe Test, the thesis was revealed in the subhead, You might not want to know all of your health results. The title refers to testing by a specific company, 23andMe, which is one of the largest direct-to-consumer genetic testing companies.

The article begins in the first person, which is ordinarily taboo in traditional journalism, but gives the article a more personal touch.

I stared at the email announcing Your 23andMe results are ready for several minutes before I had the courage to uncover my genetic health and ancestry secrets.

The article continues, talking about how more and more of these consumer genetic tests are likely to become available. The FDA has announced theyve streamlined approval, and there are several new start-ups that are ready to offer testing for your risk of cancer, genetic diseases, and, quote, an untold number of insights.

A handful of labs are working on offering a very low-cost way to sequence your entire genome, perhaps for as little as $100, in the next few years. Yet experts worry, to quote the article directly again, that consumers might be psychologically unprepared to handle frightening health information.

This is especially true about tests for diseases that currently have no cure, like Alzheimers or Parkinsons disease. In fact, the FDA approval of 23andMes health tests explicitly requires consumers to opt in to testing for these kinds of conditions.

Learn more abouthealth, medicine, and the media.

And, again, theres the crucial importance of understanding that these tests do not make a diagnosis. They can only predict a risk level. The Huffington Post article did say that toward the end, but what it didnt say is that we cannot be sure of the accuracy of these risk estimates.

So what did the authors testing show? The 23andMe material said shed have a 5%-7% chance of having Alzheimers by age 75. But we should take a look at the context the article didnt provide. According to the Alzheimers Association, the risk of having Alzheimers in the 65-74 year age range is between 3% and 9%. The evaluated risk is not much more accurate than the general estimate.

So, the media will often tell you the result of tests but not the complete context. The consumer and the reader should always know the caveats and the pitfalls.

The Centers for Disease Control is cautious about genetic testing because there is generally very little evidence about the ability of genetic information to change health behavior.

Some genetic testing services claim that their tests can predict how well an individual will respond to different medications or even to different kinds of exercise, or which foods you should eat, or even which types of wine you might prefer.

The FDA wants customers to opt in for genetic tests for diseases which have no cure or prevention, such as Alzheimers or Parkinsons disease. This is because consumers might be psychologically unprepared to handle frightening health information.

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Caveats in Genetic Testing: Reporting in the Media - The Great Courses Daily News

Cell Biology

Catamaran Bio Launches with $42 Million Financing to Develop OfftheShelf CAR-NK Cell Therapies to Treat Solid Tumors – BioSpace

In assembling the founding team at Catamaran, we saw an opportunity to pioneer a highly differentiated approach to develop allogeneic cell therapies using CAR-NK cells, said Houman Ashrafian, Managing Partner, SV Health Investors and a founder of Catamaran. To date, the success of autologous CAR T-cell therapies in hematological malignancies has opened the door to the breakthrough potential of cell therapies for cancer, and Catamaran is now well positioned to improve upon this groundwork by developing off-the-shelf CAR-NK cell therapies capable of reaching solid tumors.

A novel approach to developing off-the-shelf cell therapies to address solid tumors

Catamarans TAILWIND Platform integrates proprietary capabilities to create novel, allogeneic CARNK cell therapies by harnessing the natural cancer-fighting properties of natural killer (NK) cells and enhancing them with the power of synthetic biology and innovative NK cell engineering and manufacturing. With the TAILWIND Platform, CAR-NK cells are programmed with NK cell-specific CAR architectures and potency-boosting switches to neutralize the hostile tumor microenvironment and enable efficacy against diverse cancer types, especially solid tumors. Additionally, the TAILWIND Platform includes proprietary, non-viral NK cell engineering technology for efficient modification of NK cells with customized genetic programs enabled by synthetic biology. Catamarans CAR-NK cell therapies use healthy donor cells that are engineered and manufactured for offtheshelf use, unlike current CAR-T cell therapies that use a patients own genetically modified T cells and require a customized, multi-week manufacturing process.

Catamaran is focused on expanding the frontier of cell therapies to treat solid tumors and provide transformative benefit to cancer patients. We are doing this by creating allogeneic cell therapies that harness the innate cancer-fighting power of NK cells and enhancing them with new biologically-powerful attributes from our leading-edge technologies all originating from our custom-built TAILWIND Platform for designing, engineering and manufacturing off-the-shelf CAR-NK cell therapies, said Vipin Suri, PhD, MBA, Chief Scientific Officer of Catamaran.

During Catamarans stealth period, the start-up team assembled key components of the TAILWIND Platform and related intellectual property, including a set of potency-boosting cellular switches to enable therapeutic action in the immunosuppressive tumor microenvironment of solid tumors, and it generated early proof of concept using a non-viral transposon system to efficiently deliver large genetic cargos into NK cells. Based on this early work, the company has rapidly advanced two lead CAR-NK cell therapy programs to lead optimization stage.

With its holistic and cutting-edge approach, Catamaran stands out in the rapidly-evolving NK cell field with a platform that addresses the full complement of capabilities necessary to develop CAR-NK cell therapies, while focusing on the high-impact technologies of synthetic biology and innovative gene delivery systems that can enable these new cell therapies to offer extraordinary value in the field of cancer treatment, said Maina Bhaman, Partner, Sofinnova Partners.

Scientific founders and leadership team

Catamarans scientific founders are pioneers in NK cell biology, engineering, manufacturing and clinical application and are proven innovators in the cell therapy field:

Additional founders of Catamaran are Kevin Pojasek, PhD, and Tim Harris, PhD, through their roles as venture partners with SV Health Investors.

The leadership team at Catamaran Bio has deep expertise in cell therapy research and product development, and the team includes: Vipin Suri, PhD, MBA, Chief Scientific Officer, who has more than 20 years of biopharmaceutical experience, including as a co-founder of Obsidian Therapeutics and Serien (formerly Raze) Therapeutics, and earlier in R&D roles at GSK, Pfizer and Wyeth; Mark Boshar, JD, Chief Operating Officer, who has more than 25 years of leadership experience spanning legal, business development, financings and operations for biotechnology companies, including as VP, Legal Affairs at Rubius Therapeutics, Associate General Counsel at Millennium Pharmaceuticals, a senior advisor to a range of venture-backed start-up companies, and earlier as a life sciences attorney with WilmerHale; Chris Carpenter, MD, PhD, Chief Medical Officer, who has 20 years of clinical and laboratory experience in oncology, including as CMO of Rubius Therapeutics, SVP and Head of Cancer Epigenetics Discovery at GSK, and roles at Merck and Harvard Medical School/Beth Israel Deaconess Medical Center; Celeste Richardson, PhD, Senior VP of Research, who has 16 years of experience in research and drug discovery in biotechnology and pharmaceutical companies, including at Obsidian Therapeutics and Novartis; and Bharat Reddy, PhD, MPhil, MA, Senior Director of Business Development, who has served as director of business development at bluebird bio, as well as roles at SV Health Investors and ClearView Healthcare Partners.

Catamaran is positioned to open up new territory for cancer treatments with highly potent CAR-NK cell therapies, and we are confident in the experienced leadership team and the scientific expertise that is propelling the companys research and development, said Caroline Gaynor, Principal, Lightstone Ventures.

Concurrent with the Series A financing, Maina Bhaman of Sofinnova Partners, Caroline Gaynor of Lightstone Ventures and Rob Woodman of Takeda Ventures join Houman Ashrafian and Kevin Pojasek on the Catamaran board of directors.

About Catamaran Bio

Catamaran Bio is developing novel, off-the-shelf CAR-NK cell therapies designed to treat a broad range of cancers, including solid tumors. Our proprietary capabilities enable us to harness the natural cancer-fighting properties of NK cells and enhance and tailor their effectiveness with the power of synthetic biology and innovative non-viral cell engineering. We are using our TAILWINDTM Platform, an integrated suite of technologies, to specifically address the end-to-end methods of engineering, processing and manufacturing NK cells and rapidly advance our pipeline of CAR-NK cell therapy programs.

Our team combines experienced biopharmaceutical leadership with founding scientists who are pioneers in NK cell biology, engineering, manufacturing and clinical application. Catamaran is backed by leading financial and corporate investors, including SV Health Investors, Sofinnova Partners, Lightstone Ventures, Takeda Ventures and Astellas Venture Management. For more information, please visit http://www.catamaranbio.com and follow us on LinkedIn and @CatamaranBio on Twitter.

View source version on businesswire.com: https://www.businesswire.com/news/home/20201123005485/en/

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Catamaran Bio Launches with $42 Million Financing to Develop OfftheShelf CAR-NK Cell Therapies to Treat Solid Tumors - BioSpace

Cell Biology

Real Time Spying on the Symphony of Cellular Signals That Drive Biology – SciTechDaily

To visualize cellular signals within a neuron, researchers scattered reporters in clusters (green) across the cell. They then identified the signal each cluster represented (multiple colors).Credit: C. Linghu, S. Johnson et al./Cell 2020

A new imaging technology lets scientists spy on the flurry of messages passed within cells as they do . . . potentially everything.

Until now, most scientists could visualize only one or two of these intracellular signals at a time, says Howard Hughes Medical Institute InvestigatorEd Boyden of the Massachusetts Institute of Technology. His teams new approach could make it possible to see as many signals as you want in real time, at once, Boyden says giving researchers a more detailed view of cells internal discussions than ever before.

In tests with neurons, the researchers examined five signals involved in processes such as learning and memory, Boyden and his colleagues report today (November 23, 2020) in the journal Cell. You could apply this technology to all sorts of biological mysteries, he says. Every cell works due to all the signals inside it. Because signaling contributes to all biological processes, a better means to study it could illuminate a host of diseases, from Alzheimers to diabetes and cancer.

The teams new approach is a breakthrough, says Clifford Woolf, a neurobiologist at Harvard Medical School who was not involved with the work. He plans to use it to examine how pain-sensing neurons become more sensitive in injury or illness. With the new imaging technology, he says we can take apart whats happening in cells in a way that just has not been possible before.

Give a computer or a human brain information, and it will crackle with electrical impulses as it prepares a response. Within cells, these impulses result in spurts of multiple molecular signals. Boyden describes this process as a group conversation. Signals within a cell are like a set of people trying to decide what to do for the evening: they take into account many possibilities, and then decide what to collectively do, he says.

These cellular discussions are what prompt, for example, a neuron to encode a memory or a cell to turn cancerous. Despite their importance, scientists still dont have a strong grasp of how these signals work together to guide a cells behavior.

To see cell signaling in action, scientists typically introduce genes encoding sensors connected to fluorescent proteins. These molecular reporters sense a signal and then glow a specific color under the microscope. Researchers can use a different color reporter for each signal to tell the signals apart. But finding sets of reporters with colors that a microscope can differentiate is challenging. And a typical cellular conversation can involve dozens of signals or more.

Changyang Linghu and Shannon Johnson, scientists in Boydens lab, got around this limitation by affixing reporters to small, self-assembling proteins that act like LEGO bricks. These small proteins clicked together, forming clusters that were randomly scattered across the cell like little islands. Each cluster, which appears under the microscope as a luminescent dot, reports only one type of cellular signal. Its like having some islands with thermometers to report temperature and other islands with barometers measuring pressure, Johnson says.

In experiments with neurons, the team created clusters that each glowed upon detection of one of five different signals, including calcium ions and other important signaling molecules. After imaging the live cells, the researchers attached molecular labels to the glowing dots to identify the reporters located there. Using computer analyses, the team turned the dots magenta, yellow, and other colors, depending on whether they represented calcium or another signal. This let them see which signals were switching on and off across a cells interior.

By monitoring so many signals at once, the team was able to figure out how each signal related to one another. Teasing apart such relationships could help scientists understand complex processes like learning, Linghu says.

He likens a cell to an orchestra and its signals to a symphony. Its difficult to fully appreciate a symphony by listening to just a single instrument, he says. Because the new technique lets scientists observe multiple signals at the same time, we can understand the symphony of cellular activities.

Boydens team estimates it may be possible to detect as many as 16 signals with their technology, but improvements in genetic engineering techniques could raise that number significantly. Potentially, you could look at dozens, hundreds, or even more signals, he says. The next challenge, Boyden says, is getting sensors for all of those signals into a cell.

Reference: Spatial multiplexing of fluorescent reporters for dynamic imaging of signal transduction networks by Changyang Linghu, Shannon L. Johnson et al., 23 November 2020, Cell.DOI:: 10.1016/j.cell.2020.10.035

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Real Time Spying on the Symphony of Cellular Signals That Drive Biology - SciTechDaily

Cell Biology

Post-doctoral Fellow in Computational Stem Cell Biology job with THE UNIVERSITY OF HONG KONG | 234737 – Times Higher Education (THE)

Work type:Full-timeDepartment:School of Biomedical Sciences (22600)Categories:Academic-related Staff

Applications are invited for appointment asPost-doctoral Fellow in Computational Stem Cell Biology (several posts) in the School of Biomedical Sciences(Ref.:502657), to commence as soon as possible for one to three year(s), with the possibility of renewal subject to satisfactory performance.

The selected candidates will work in a company incorporated by the University of Hong Kong that was established to administer and support the Universitys innovation endeavors. They will conduct research in a computational lab and closely work with experimental lab(s).The specific project will be discussed and determined between each candidate and the Principal Investigator together.

Applicants should have a Ph.D. degree in Bioinformatics, Genetics, Computational Biology or other relevant quantitative disciplines, and in-depth experience in at least one of the programming languages for scientific computing, for example, Python, R, Perl, C/C++ and JAVA.Research experience in stem cells, regenerative medicine, cancer, heart disease, liver disease, immunology or drug screening would be an advantage.Preference will be given to those with expertise in bioinformatics and computational biology, and with strong interests in translational research utilizing next-generation sequencing and single-cell sequencing to study any of the above research areas.The ability to work independently, participate in highly collaborative projects, and contribute intellectually to research development are requisites.Applicants should also be highly motivated individuals with good verbal and written communication skills in English.

A competitive salary commensurate with qualifications and experience will be offered.

The University only accepts online applications for the above posts. Applicants should apply online and upload an up-to-date C.V.Review of applications will start from December 4, 2020 and continue untilDecember 30, 2020, or until the posts are filled, whichever is earlier.

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Post-doctoral Fellow in Computational Stem Cell Biology job with THE UNIVERSITY OF HONG KONG | 234737 - Times Higher Education (THE)

Cell Biology

Prachee Avasthi Honored with 2020 WICB Junior Award for Excellence in Research – Newswise

Newswise Prachee Avasthi was selected by the Women in Cell Biology (WICB) of the American Society for Cell Biology for the 2020 WICB Junior Award for Excellence in Research.Avasthi is an associate professor of Biochemistry and Cell Biology at Geisel School of Medicine at Dartmouth College, though she noted that the work recognized by this award was done at the University of Kansas Medical Center, where she was until recently.

Prachee Avashthis nominator, Wallace Marshall, University of California, San Francisco, called her a star. He wrote: She has proven a willingness to use any approach necessary to pursue the most important questions, and a complete fearlessness to go against prevailing dogma. At the same time, she has proven a highly effective mentor for her trainees, and a role model for both junior and senior investigators alike. In my opinion, she perfectly represents the qualities that the ASCB WICB Junior Award for Excellence in Research seeks to encourage.

Avasthi is an associate professor of Biochemistry and Cell Biology at Geisel School of Medicine at Dartmouth College, though she noted that the work recognized by this award was done at the University of Kansas Medical Center, where she was until recently.

Using a unicellular green alga as a model system, her lab uses chemical biology, biochemistry, genetics, and quantitative live-cell imaging to uncover novel mechanisms regulating assembly of the cilium. That work led to investigation of the intersection of the microtubule and actin cytoskeleton, as well as fundamental actin dynamics and function.

She stays busy outside the lab as well. An advocate for improved publication practices, she serves on the boards of directors for ASAPbio and eLife. She also founded New PI Slack, the online peer-mentoring community for junior faculty, and is on the steering committee of Rescuing Biomedical Research.

Avasthi said, I am quite stunned to receive this award! The past winners are leaders in their fields such that none of the previous selections surprised me. Im routinely inspired by the creativity and brilliance of others, so it means a lot to me that the colleagues I so respect see the beauty that I see in the science were uncovering. I am incredibly honored and am thrilled for my lab members, whose hard work is being recognized by this award. They deserve this.

Her talk at Cell Bio Virtual 2020 will be on Cytoskeletal Diversity, Flexibility, and Functions.

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Prachee Avasthi Honored with 2020 WICB Junior Award for Excellence in Research - Newswise

Cell Biology

New study on CRISPR: the stake of unintended consequences in embryos – BioNews

23 November 2020

A recent paper published in the journalCell revealed the cautionary finding that unwanted changes are introduced after modifying genesin human embryos with CRISPR/Cas9. The study, led by Dr Dietrich Egli, assistant professor of developmental cell biology at Columbia University Vagelos College of Physicians and Surgeons, tested theeffects of CRISPR-based genome editingon embryos carrying a mutationin a gene called EYS (eyes shut homolog) which could lead to hereditary blindness. It shows that applying this potent approachto repair a blindness-causing gene in the formation of an early embryo discards the whole chromosome, or a considerable portion of it, and that the loss of the chromosome is widespread.

CRISPR-based genome editing has revolutionised molecular life sciences. It allows scientists to perform accurate modifications in the genomes of living tissues and may lead to new medical therapies such as innovative cancer treatments and curing hereditary illnesses. In October 2020, CRISPR discoverers (Professors Emmanuelle Charpentier of Max Planck Institute for Infection Biology, Germany, and Jennifer Doudna of University of California, Berkeley) were jointly awarded the Nobel Prize in chemistry.

However, like most innovative techniques, there are currently technical challenges. For example, it is possible to produce so-called off-target effects, where edits are performed in the wrong area. Researchers are still unsure as to how this might affect patients. Another concern is mosaicism, where some cells carry the edit but others do not. Such changes performed to sperm,egg and embryos can be passed to subsequent generations. In the second international summit on human genome editing, there was broad agreement among the experts in attendance that these risks are high.

Despite these serious concerns, in December 2018, Dr He Jiankui shocked the world by announcing that the first babies had been born with altered genomes (see BioNews 978). His work has attracted a backlash from the international scientific community and various governments. Dr He has been sentenced to three years in jail and fined for performing 'illegal medical practices'.

The new research indicates that CRISPR genome editing is currently not ready for clinical application to correct mutations in this early phase of human development. These findings should deter premature clinical use of genome editing on embryos. Thus, using CRISPR to edit the genomes of embryos is a far-off reality.

Due to the serious ethical concerns, the US government does not allow the use of federal funds to perform research on human embryos. The experiment was sponsored by private funding (the New York Stem Cell Foundation and the Russell Berrie Foundation programme). In Australia, section 15 of the Prohibition of Human Cloning for Reproduction Act 2002 prohibits a person from altering the genome of a human embryo in such a manner that the change is heritable by its descendantsandthe person intended this to be so. The penaltyfor this offence is imprisonment for 15 years.

We need to guide responsible and ethical research to achieve safe and effective use. In November 2020, the members of the International Society for Stem Cell Research (ISSCR) task force were charged with revising the2016 ISSCR Guidelines (the Guidelines for Stem Cell Research and Clinical Translation). The ISSCR is the largest stem cell organisation in the world. As a contribution to the developing and controversial stem cell field, this organisation has developed guidelines that address the global diversity of ethical, legal, ethical, cultural and political perspectives related to stem cell research and its translation to clinical application. The guidelines underscore widely shared principles that call for rigour, oversight and transparency. Strict adherence to these principles assures that such cutting-edge research is being conducted with integrity and that innovative medical treatments are evidence-based. Recent advances in this field include innovations in genome editing, organoidsand chimeras. Responding to these various developments in science, the updates will encompass a broader and more expansive scope of research and clinical endeavour, imposing rigour on every stage of the study, addressing the cost of regenerative medicine products and stressing the need for precise and effective public communication.

The persuasive ISSCR Guidelines have been adopted by some scientists, clinicians and institutions around the world. While mere guidelines do not supersede local laws, they could inform the interpretation as well as the development of local laws and provide guidance for research practices not covered by the law. As these guidelines will be updated soon, it is important that they do not encourage the clinical application of the CRISPR approach on genome-editing human embryos for the time being.

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New study on CRISPR: the stake of unintended consequences in embryos - BioNews

Cell Biology

Basic concepts lay the foundation for personalized immunotherapy – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Nov 23 2020

Personalized Immunotherapy for Tumor Diseases and Beyond introduces personalized immunotherapy with multi-dimensional models of analysis to determine the best plan for the immunotherapy of patients.

The book introduces readers to some basic concepts which lay the foundation for personalized immunotherapy: the development of a major histocompatibility complex (MHC), the genome profile of T cells and tumor cells, and genome-wide association studies. Chapters also cover special topics such as new immunoassay methods related to personalized immunotherapy and targeted immunotherapy which are geared towards familiarizing readers with current research practices.

Focusing on the central theme of personalized immunotherapy, the authors provide a wealth of information about T-cell screening, tumor neoantigen cloning, primary tumor cell culture for T-cell cloning, bioinformatics strategies for understanding T-cell and primary tumor cell biology and function, and new developments in research on adoptive T-cell immunotherapy.

These developments include T-cell gene therapy and T-cell gene editing, transgenic T-cells for increasing affinity to tumor cells such as CAR T-cells and TCR T-cells, and the systematic modeling of polyclonal specific T-cells and biobank technology.

Personalized Immunotherapy for Tumor Diseases and Beyond is an ideal handbook for medical professionals and students involved in personalized medicine, immunology, and oncology. General readers interested in the new developments in these fields will also benefit from the information provided.

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Basic concepts lay the foundation for personalized immunotherapy - News-Medical.Net

Cell Biology

Star-Shaped Brain Cells May Hold the Key to Why and How We Sleep – SciTechDaily

Astrocytes in the brain expressing a fluorescent calcium indicator captured with a two-photon microscope. Credit: Image by Ashley Ingiosi, courtesy of Current Biology

A study published in the journal Current Biology suggests that star-shaped brain cells known as astrocytes could be as important to the regulation of sleep as neurons, the brains nerve cells.

Led by researchers at Washington State Universitys Elson S. Floyd College of Medicine, the study builds new momentum toward ultimately solving the mystery of why we sleep and how sleep works in the brain. The discovery may also set the stage for potential future treatment strategies for sleep disorders and neurological diseases and other conditions associated with troubled sleep, such as PTSD, depression, Alzheimers disease, and autism spectrum disorder.

What we know about sleep has been based largely on neurons, said lead author and postdoctoral research associate Ashley Ingiosi. Neurons, she explained, communicate through electrical signals that can be readily captured through electroencephalography (EEG). Astrocytesa type of glial (or glue) cell that interacts with neuronsdo not use electrical signals and instead use a process known as calcium signaling to control their activity.

It was long thought that astrocyteswhich can outnumber neurons by five to onemerely served a supportive role, without any direct involvement in behaviors and processes. Neuroscientists have only recently started to take a closer look at their potential role in various processes. And while a few studies have hinted that astrocytes may play a role in sleep, solid scientific tools to study their calcium activity have not been available until recently, Ingiosi said.

To delve deeper into astrocytes role in sleep, she and her coauthors used a rodent model to record astrocytes calcium activity throughout sleep and wake, as well as after sleep deprivation. They used a fluorescent calcium indicator that was imaged via tiny head-mounted microscopes that looked directly into the brains of mice as they moved around and behaved as they normally would. This indicator allowed the team to see calcium-driven fluorescent activity twinkling on and off in astrocytes during sleep and waking behaviors. Their one-of-a-kind methodology using these miniature microscopes allowed the team to conduct the first-ever study of astrocytes calcium activity in sleep in freely behaving animals.

The research team set out to answer two main questions: do astrocytes change dynamically across sleep and wake states like neurons do? And do astrocytes play a role in regulating sleep need, our natural drive to sleep?

Looking at astrocytes in the frontal cortex, an area of the brain associated with measurable EEG changes in sleep need, they found that astrocytes activity changes dynamically across the sleep-wake cycle, as is true for neurons. They also observed the most calcium activity at the beginning of the rest phasewhen sleep need is greatestand the least calcium activity at the end of the rest phase, when the need for sleep has dissipated.

Next, they kept mice awake for the first 6 hours of their normal rest phase and watched calcium activity change in parallel with EEG slow wave activity in sleep, a key indicator of sleep need. That is, they found that sleep deprivation caused an increase in astrocyte calcium activity that decreased after mice were allowed to sleep.

Their next question was whether genetically manipulating astrocyte calcium activity would impact sleep regulation. To find out, they studied mice that lacked a protein known as STIM1 selectively in astrocytes, which reduced the amount of available calcium. After being sleep deprived, these mice did not sleep as long or get as sleepy as normal mice once allowed to sleep, which further confirmed earlier findings that suggest that astrocytes play an essential role in regulating the need for sleep.

Finally, they tested the hypothesis that perhaps astrocyte calcium activity merely mirrors the electrical activity of neurons. Studies have shown that the electrical activity of neurons becomes more synchronized during non-REM sleep and after sleep deprivation, but the researchers found the opposite to be true for astrocytes, with calcium activity becoming less synchronized in non-REM sleep and after sleep deprivation.

This indicates to us that astrocytes are not just passively following the lead of neurons, said Ingiosi. And because they dont necessarily display the same activity patterns as neurons, this might actually implicate a more direct role for astrocytes in regulating sleep and sleep need.

More research is needed to further unravel the role of astrocytes in sleep and sleep regulation, Ingiosi said. She plans to study astrocytes calcium activity in other parts of the brain that have been shown to be important for sleep and wake. In addition, she would like to look at astrocytes interactions with different neurotransmitters in the brain to start to tease out the mechanism by which astrocytes might drive sleep and sleep need.

The findings of our study suggest that we may have been looking in the wrong place for more than 100 years, said senior author and professor of biomedical sciences Marcos Frank. It provides strong evidence that we should be targeting astrocytes to understand why and how we sleep, as well as for the development of therapies that could help people with sleep disorders and other health conditions that involve abnormal sleep.

Reference: A Role for Astroglial Calcium in Mammalian Sleep and Sleep Regulation by Ashley M. Ingiosi, Christopher R. Hayworth, Daniel O. Harvey, Kristan G. Singletary, Michael J. Rempe, Jonathan P. Wisor and Marcos G. Frank, 24 September 2020, Current Biology.DOI: 10.1016/j.cub.2020.08.052

Support for the study came from the National Institutes of Health.

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Star-Shaped Brain Cells May Hold the Key to Why and How We Sleep - SciTechDaily

Cell Biology

Five Salk professors named among most highly cited researchers in the world – Salk Professors Joanne Chory Joseph Ecker Rusty Gage Reuben Shaw and Kay…

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Salk ProfessorsJoanne Chory,Joseph Ecker,Rusty Gage,Reuben ShawandKay Tyehave been named to theHighly Cited Researchers listby Clarivate. The list identifies researchers who demonstrate significant influence in their chosen field or fieldsthrough the publication of multiple highly cited papers.Professors Chory, Ecker and Gage have been named to this list every year since 2014, when the regular annual rankings began. This is Professor Tyes fourth consecutive time and Professor Shaws second consecutive time receiving the designation. Joseph Nery, a research assistant II in the Ecker lab, was also included on the list.

In the race for knowledge, it is human capital that isfundamentaland this list identifies and celebrates exceptional individual researchers who are having a great impact on the research community as measured by the rate at which their work is being cited by others,says David Pendlebury, senior citation analyst at the Institute for Scientific Information, part of the Web of Science group at Clarivate.

Such consistent production of highly cited reports indicates that the work of these researchers has been repeatedly judged by their peers to be of notable significance and utility, as based on data from the Web of Science, the worlds largest publisher-neutral citation index, with almost 1.9 billion cited references going back to 1900. This years list, which includes 6,167 researchers from more than 60 countries, recognizes researchers across multiple fields whose citation records position them in the highest ranks of influence.

Joanne Chory

Chory is a professor in, and director of, Salks Plant Molecular and Cellular Biology Laboratory, a Howard Hughes Medical Institute investigator, and holder of the Howard H. and Maryam R. Newman Chair in Plant Biology. Chory has won numerous prestigious awards for her work including the Gruber Genetics Prize and the Breakthrough Prize. She also co-directs SalksHarnessing Plants Initiativea bold approach to address climate changeby optimizing a plants natural ability to capture and store carbon and adapt to diverse climate conditions.

Joseph Ecker

Ecker is a professor in Salks Plant Molecular and Cellular Biology Laboratory, director of the Genomic Analysis Laboratory and a Howard Hughes Medical Institute investigator. He is also the Salk International Council Chair in Genetics. He was the first to show that the epigenome is highly dynamic in brain cells during the transition from birth to adulthood. Ecker is the recipient of multiple recentNational Institutes of Health BRAIN Initiative grants, and he is charting the epigenetic differences between brain cell types to better understand disorders such as schizophrenia and Alzheimers disease.

Rusty Gage

Gage, a professor in the Laboratory of Genetics and holder of the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease, is the president of the Salk Institute. He discovered that the adult brain continues to produce new neurons throughout the life span in a process known as neurogenesis. Most recently, he, and a team of Salk researchers were awarded anAmerican Heart Association-Allen Initiative in Brain Healthgrant to pursue a new collaborative approach to understanding, detecting and potentially treating Alzheimers disease and age-related cognitive decline.

Reuben Shaw

Shaw, a professor in the Molecular and Cell Biology Laboratory and holder of the William R. Brody Chair, is the director of the Salk Cancer Center, a recipient of the National Cancer Institute Outstanding Investigator Award, and leads SalksConquering Cancer Initiative. He discovered direct connections between cancer and metabolism and continues to work on how nutrient deprivation and cellular energy levels control cancer and other diseases.

Kay Tye

Tye is a professor in Salks Systems Neurobiology Laboratory and holder of the Wylie Vale Chair. Sheseeks to understand the neural-circuit basis of emotion that leads to motivated behaviors such as social interaction, reward-seeking and avoidance. Last year, she published a seminal paper describing herdiscovery of a brain circuit that controls alcohol drinkingbehavior in mice and can be used as a biomarker for predicting the development of compulsive drinking later on. This year, she published work furthering her investigation on the neural circuits associated with the experience of loneliness.

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Five Salk professors named among most highly cited researchers in the world - Salk Professors Joanne Chory Joseph Ecker Rusty Gage Reuben Shaw and Kay...