Daily Archives: January 9, 2022

23ME-00610 targets CD200R1, an important regulator of T cells and myeloid cells

CD200R1 was identified as a promising immuno-oncology target through 23andMes proprietary genetic and health survey database

Company will host a virtual R&D Day event on January 18, 2022

SUNNYVALE, Calif., Jan. 06, 2022 (GLOBE NEWSWIRE) -- 23andMe Holding Co. (Nasdaq: ME) (23andMe), a leading consumer genetics and research company, today announced the first participant has been dosed in a Phase 1 clinical trial evaluating 23ME-00610 for the treatment of advanced solid tumors. 23ME-00610 is 23andMes first wholly-owned immuno-oncology (I/O) antibody to enter the clinic. The target for the new investigational antibody, CD200R1, was identified as a promising immuno-oncology target through 23andMes proprietary genetic and health survey database.

This is an important milestone for 23andMe in our mission to help people access, understand and benefit from the human genome, said Anne Wojcicki, CEO and co-founder, 23andMe. When we started our Therapeutics group, our goal was to find new medicines validated by human genetics for people with serious unmet medical needs. Thats why were excited to move 23ME-00610 into the clinic to potentially help people with cancer who are in need of new treatment options.

The Phase 1 clinical trial is designed to evaluate the safety, tolerability and pharmacokinetics of 23ME-00610 in patients with locally advanced or metastatic solid tumors whose disease has progressed after standard of care treatment. 23ME-00610 is part of 23andMes larger drug discovery program of targets validated by human genetics across a spectrum of disease areas, including oncology, immunology, respiratory, and cardiometabolic diseases.

Our approach to drug discovery is driven by human genetics, and we have an incredibly large database from which to select and advance genetically validated targets more efficiently, and with a potentially higher probability of success, than traditional drug discovery methods currently allow, said Kenneth Hillan, Head of Therapeutics at 23andMe. 23ME-00610 is an exciting example of how we are translating our data into investigational therapeutics.

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23andMe has approximately 12 million customers, approximately 80% of whom consent to participate in research. 23andMe scientists study aggregate, de-identified genetics of these participants, alongside more than 4 billion health survey answers. Using its large database of genetically linked health traits and machine learning applied to its proprietary I/O genetic signature, 23andMe is able to pinpoint areas of the genome that contain targets for cancer therapeutics based on human genetics, including the 23ME-00610 target.

23andMes Immuno-oncology genetic signatureUsing its genetic data, 23andMe can identify immune-related genes that are expected to have an impact on cancer biology. Specifically, germline genetics can reveal which of the immune-related genes harbor genetic variants that also alter an individual's predisposition for developing cancer. 23andMe has developed an analytical approach, termed the immuno-oncology (I/O) genetic signature, to identify evidence for genetic variants that increase immune function while decreasing cancer risk. Using this approach, 23andMe scientists discovered that three components of the CD200R1 pathway exhibit an I/O genetic signature, including the CD200R1 receptor, the CD200 ligand, and DOK2, a mediator of downstream signaling from CD200R1. Following this genetic insight, 23andMe subsequently generated data consistent with CD200R1s role in inhibiting anti-tumor responses in immune cells.

About CD200R1 and 23ME-00610The CD200CD200R1 axis is an immunological checkpoint that plays a pivotal role in maintenance of immune tolerance. CD200R1 is an inhibitory receptor expressed on T cells and myeloid cells while CD200, the ligand for CD200R1, is highly expressed on certain tumors. Binding of tumor associated CD200 to CD200R1 leads to immune suppression and decreased immune cell killing of cancer cells.

23ME-00610 is a high-affinity humanized monoclonal antibody that is designed to bind to the CD200R1 receptor and prevent the interaction of CD200 and CD200R1. Preclinical data indicate that this mechanism has the potential to reinvigorate tumor-exhausted T-cells and myeloid cells to restore their ability to kill cancer cells.

About the Phase 1 23ME-00610 StudyThe first-in-human, multi-center, open-label clinical trial will determine the safety and tolerability of 23ME-00610 in people with locally advanced or metastatic solid malignancies that have progressed after standard therapy. This study will also evaluate preliminary anticancer activity, and the pharmacokinetic and pharmacodynamic profile of 23ME-00610 to identify the optimal dose and schedule for further clinical studies. After the Phase I dose escalation phase is completed, 23andMe will seek to enroll people with specific tumor types to evaluate the potential for anticancer efficacy and changes in pharmacodynamic endpoints in the expansion phase.

Participants with ECOG performance status 0-1, and with histologically diagnosed locally advanced or metastatic solid malignancy that has progressed after standard therapy for the specific tumor type are eligible. Additionally, adolescents 12 years and older with histologically diagnosed locally advanced, or metastatic solid malignancy are eligible for enrolment in the expansion phase.

R&D Day Event InformationTo discuss 23ME-00610 and other developments from its Therapeutics group in more detail, the company will host a virtual R&D Day event from 8:00 a.m. to 11:30 am Pacific Time on Tuesday, January 18, 2022. The webcast event can be accessed on the day of the event at https://investors.23andme.com/news-events/events-presentations. A webcast replay will be available at the same address for a limited time within 24 hours after the event.

About 23andMe23andMe, headquartered in Sunnyvale, CA, is a leading consumer genetics and research company. Founded in 2006, the companys mission is to help people access, understand, and benefit from the human genome. 23andMe has pioneered direct access to genetic information as the only company with multiple FDA authorizations for genetic health risk reports. The company has created the worlds largest crowdsourced platform for genetic research, with ~ 80 percent of its customers electing to participate. The 23andMe research platform has generated more than 180 publications on the genetic underpinnings of a wide range of diseases, conditions, and traits. The platform also powers the 23andMe Therapeutics group, currently pursuing drug discovery programs rooted in human genetics across a spectrum of disease areas, including oncology, respiratory, and cardiovascular diseases, in addition to other therapeutic areas. More information is available at http://www.23andMe.com.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements, other than statements of historical fact, included or incorporated in this press release, including statements regarding 23andMes strategy, financial position, funding for continued operations, cash reserves, projected costs, plans and objectives of management, clinical trials and the potential outcomes and timing thereof, the identification and advancement of genetically validated targets, and the potential or success of any such genetically validated targets, are forward-looking statements. The words "believes," "anticipates," "estimates," "plans," "expects," "intends," "may," "could," "should," "potential," "likely," "projects," predicts, "continue," "will," schedule, and "would" or, in each case, their negative or other variations or comparable terminology, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are predictions based on 23andMes current expectations and projections about future events and various assumptions. 23andMe cannot guarantee that it will actually achieve the plans, intentions, or expectations disclosed in its forward-looking statements and you should not place undue reliance on 23andMes forward-looking statements. These forward-looking statements involve a number of risks, uncertainties (many of which are beyond the control of 23andMe), or other assumptions that may cause actual results or performance to differ materially from those expressed or implied by these forward-looking statements. The forward-looking statements contained herein are also subject to other risks and uncertainties that are described in 23andMes Quarterly Report on Form 10-Q for the quarter ended September 30, 2021 filed with the Securities and Exchange Commission (SEC) on November 10, 2021 and in the reports subsequently filed by 23andMe with the SEC. The statements made herein are made as of the date of this press release and, except as may be required by law, 23andMe undertakes no obligation to update them, whether as a result of new information, developments, or otherwise.

Contacts:Investor Relations: investors@23andMe.comMedia: press@23andMe.com

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23andMe Initiates Phase 1 Clinical Trial for First Wholly-Owned Immuno-oncology Antibody for Patients with Solid Tumors - Yahoo Finance

NEW YORK A Chinese-Italian research team has developed a new open-source genetic reporting tool for individuals who have obtained their own genomic data from consumer genomics providers.

Called Personal Access to Genome and Analysis of Natural Traits, or PAGEANT, the platform enables users to analyze and interpret their genomic data at no cost. Both SNP array and next-generation sequencing data can be analyzed using the new resource, which was described in a Nucleic Acids Research paper published last month.

The collaboration that produced PAGEANT evolved out of a relationship between scientists at the University of Camerino in Italy and the Peking University School of Public Health in Beijing. According to corresponding author Valerio Napolioni, a geneticist at the University of Camerino, he previously cooperated with Jie Huang's group at Peking University to produce a tool called PERHAPS that supports paired-end short reads-based haplotyping from next-generation sequencing data. PAGEANT is the result of several projects that are underway.

"We both studied human genomics and were interested in creating a free and reliable version of a genome interpretation tool, which is essential for science to be translated into health and knowledge," said Huang.

The argument that people holding their genomic data, acquired via ancestry and health and wellness providers such as Ancestry, 23andMe, MyHeritage, or Family Tree DNA, are not being well served is a central tenet of PAGEANT's creators. This is no small number. According to the paper, as of 2018, more than 25 million people worldwide had taken one of these consumer tests.

However, even though scientists have been churning out loci of interest via nearly infinite genome-wide association studies over the past decade and a half, the researchers maintain in the paper that insights gleaned from these studies have yet to sufficiently make it into public use.

"The public lack the means to avail such data for interpretation of their own genomes," the authors write in the new paper. Direct-to-consumer testing, meanwhile, is "under strict government regulation" and faces multiple challenges, such as concerns around psychological impact, lack of access to genetic counseling, and the lack of validity or utility of results.

There does exist an extensive menu of free academic third-party tools for generating similar results and which vary in scope and accessibility. The new paper identifies nearly 30 of such tools that have existed, although the list continues to fluctuate as new ones are deployed and older ones are deactivated. For instance, DNA.Land, a data upload site that provided free ancestry and trait reports and cousin matching, went offline in November. Other sites, such as Promethease, recently transitioned into a for-profit model and were not considered a direct competitor to PAGEANT. Interpretome, a somewhat similar tool, has also been deactivated.

In the paper, the researchers identified two tools in existence that were the most similar, Impute.me and openSNP. Impute.me was developed by Danish researchers at Sankt Hans Hospital in Roskilde in 2015. OpenSNP was developed by a German research team in 2011.

PAGEANT's makers benchmarked the new tool against Impute.me in the development process.

They also used genome data from the 1000 Genomes Project as well as GWAS summary statistical data from the COVID-19 Host Genetics Initiative. They were supported financially by the National Key Research and Development Program of China and the Peking University Research Initiation Fund, as well as Innova Package, a Fujian, China-based company, and somepersonal funds.

Huang said that PAGEANT is different from most tools out there, commercial or third party, because of its privacy and security features, as well as its ability for customization. "We value the confidentiality of human genome data," noted Huang. "Therefore, PAGEANT can be run locally without sending any data to a remote server," he said. In addition, each line of PAGEANT's source code is open, and its analysis tool can be refitted as new scientific papers are published.

"If a user feels that it is more accurate to predict his genetic risk for lung cancer based on a million genetic variants reported by a new paper, he could easily do that in PAGEANT," he said.

The ACGTU philosophy and 5Q design

PAGEANT is organized around five philosophies, according to the authors, which they summarize as ACGTU, the five letters for nucleic acids. A stands for academic quality and standards. C is for confidential data run locally. G refers to a generalizable architecture and algorithm. T is for the transparency of its source code, and U stands for user-centric, as users can add or move traits from a genetic report.

These five philosophies are combined with what the authors call PAGEANT's 5Q design. The 5 "Qs" are quality control of genetic data; qualitative assessment of genetic characteristics of absolute or high uncertainty; quantitative assessment of health risk susceptibility based on polygenic risk scores; querying of third-party variants databases such as ClinVAR and PharmGKB; and generating secure quick response codes for tagging individual genomes.

Huang called PAGEANT's ACGTU philosophy and 5Q design approach "revolutionary" and said the researchers hope their perspective and methods will "gradually be viewed as a standard by the DTC field."

Additional activities related to PAGEANT are in progress, Huang noted. The researchers have secured an undisclosed amount of funding from Peking University to establish PAGEANT.me, and they will continue to improve the platform. Huang stressed that since PAGEANT runs on a user's desktop, it does not collect data from users for use in other genetic studies, for example.

"We understand that a users genetic data is confidential and private, and we have no intention and it is none of our business to collect any data," said Huang. "We simply want to promote an academic [tool] that hopefully could be widely adopted."

A valuable addition

Cathryn Lewis, a professor of genetic epidemiology and statistics at King's College London, is familiar with third-party analysis tools and polygenic risk scores. She co-authored a review of such tools in the journal Genome Medicine last year. She has also collaborated with Lasse Folkersen, one of the developers of Impute.me, and this month published a tool for translating polygenic scores onto the absolute scale using summary statistics in the European Journal of Human Genetics.

When asked about PAGEANT, Lewis called the platform a "valuable addition to the open-source, open-access landscape." According to Lewis, the need for tools like PAGEANT, as well as Impute.me, "highlights a growing discontinuity in the provision of genetic data." While whole-genome sequencing for rare disorders is becoming ubiquitous, Lewis said that tests that link common variation to complex diseases are not yet widely available.

"This leaves people to seek information on their genetic susceptibility through direct-to-consumer providers, and then use independent software for polygenic scores," said Lewis.

Also, while tools like PAGEANT might provide accurate information to users, Lewis said that it is still unknown how people are interpreting their results, and if the reports of increased or decreased risk are leading to increased sharing of data with clinical providers or changes in lifestyle. She noted that a score in the 90th percentile might be alarming to a user, but one in 10 people will have a similar or higher risk score.

"In interpreting a polygenic score, knowing where our score lies relative to others is a core piece of information," said Lewis. Users should therefore know their relative risk compared to the population prevalence, as well as their absolute risk. "Accurate software is only the first piece of giving risk information, and it is essential to be paired with clear communication of how to interpret our results," Lewis said.

Sarah Nelson, a research scientist at the University of Washington's department of biostatistics, authored a review of third-party genetic interpretation tools in 2018 in the Journal of Genetic Counseling. She noted that there is "a lot of flux" in terms of available tools, as new ones appear and others are shuttered over time.

"Even though third-party tools aren't going away as a class of consumer products, there have been a lot of changes," said Nelson, noting that DNA.Land shut down in November, and that GEDmatch was acquired by Verogen, a forensics company, in December 2019.

"Tools come and go, they are more transient than DTC companies, though there is flux in that market as well," Nelson pointed out. She added that such volatility could be "worrisome" for users who choose to upload their data to such sites that collect anonymized raw data, an issue that PAGEANT has addressed by allowing users to run the analysis locally on their desktops.

"Even if this tool goes away in two years, it's not like they have thousands of raw data profiles sitting on a server somewhere," Nelson said.

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International Team Debuts New Platform for DIY Genetic Analysis and Interpretation - GenomeWeb

The sweetness of sugar is one of life's great pleasures. People's love for sweet is so visceral, food companies lure consumers to their products by adding sugar to almost everything they make: yogurt, ketchup, fruit snacks, breakfast cereals and even supposed health foods like granola bars.

Schoolchildren learn as early as kindergarten that sweet treats belong in the smallest tip of the food pyramid, and adults learn from the media about sugar's role in unwanted weight gain. It's hard to imagine a greater disconnect between a powerful attraction to something and a rational disdain for it. How did people end up in this predicament?

Insights into our species' evolutionary history can provide important clues about why it's so hard to say no to sweet.

The basic activities of day-to-day life, such as raising the young, finding shelter and securing enough food, all required energy in the form of calories. Individuals more proficient at garnering calories tended to be more successful at all these tasks. They survived longer and had more surviving children - they had greater fitness, in evolutionary terms.

One contributor to success was how good they were at foraging. Being able to detect sweet things - sugars - could give someone a big leg up.

In nature, sweetness signals the presence of sugars, an excellent source of calories. So foragers able to perceive sweetness could detect whether sugar was present in potential foods, especially plants, and how much.

This ability allowed them to assess calorie content with a quick taste before investing a lot of effort in gathering, processing and eating the items. Detecting sweetness helped early humans gather plenty of calories with less effort. Rather than browsing randomly, they could target their efforts, improving their evolutionary success.

Sweet taste genesEvidence of sugar detection's vital importance can be found at the most fundamental level of biology, the gene. Your ability to perceive sweetness isn't incidental; it is etched in your body's genetic blueprints. Here's how this sense works.

Sweet perception begins in taste buds, clusters of cells nestled barely beneath the surface of the tongue. They're exposed to the inside of the mouth via small openings called taste pores.

Different subtypes of cells within taste buds are each responsive to a particular taste quality: sour, salty, savory, bitter or sweet. The subtypes produce receptor proteins corresponding to their taste qualities, which sense the chemical makeup of foods as they pass by in the mouth.

One subtype produces bitter receptor proteins, which respond to toxic substances. Another produces savory (also called umami) receptor proteins, which sense amino acids, the building blocks of proteins. Sweet-detecting cells produce a receptor protein called TAS1R2/3, which detects sugars. When it does, it sends a neural signal to the brain for processing. This message is how you perceive the sweetness in a food you've eaten.

Genes encode the instructions for how to make every protein in the body. The sugar-detecting receptor protein TAS1R2/3 is encoded by a pair of genes on chromosome 1 of the human genome, conveniently named TAS1R2 and TAS1R3.

Comparisons with other species reveal just how deeply sweet perception is embedded in human beings. The TAS1R2 and TAS1R3 genes aren't only found in humans - most other vertebrates have them, too. They're found in monkeys, cattle, rodents, dogs, bats, lizards, pandas, fish and myriad other animals. The two genes have been in place for hundreds of millions of years of evolution, ready for the first human species to inherit.

Geneticists have long known that genes with important functions are kept intact by natural selection, while genes without a vital job tend to decay and sometimes disappear completely as species evolve. Scientists think about this as the use-it-or-lose-it theory of evolutionary genetics. The presence of the TAS1R1 and TAS2R2 genes across so many species testifies to the advantages sweet taste has provided for eons.

The use-it-or-lose-it theory also explains the remarkable discovery that animal species that don't encounter sugars in their typical diets have lost their ability to perceive it. For example, many carnivores, who benefit little from perceiving sugars, harbor only broken-down relics of TAS1R2.

Sweet taste liking

The body's sensory systems detect myriad aspects of the environment, from light to heat to smell, but we aren't attracted to all of them the way we are to sweetness.

A perfect example is another taste, bitterness. Unlike sweet receptors, which detect desirable substances in foods, bitter receptors detect undesirable ones: toxins. And the brain responds appropriately. While sweet taste tells you to keep eating, bitter taste tells you to spit things out. This makes evolutionary sense.

So while your tongue detects tastes, it is your brain that decides how you should respond. If responses to a particular sensation are consistently advantageous across generations, natural selection fixes them in place and they become instincts.

Such is the case with bitter taste. Newborns don't need to be taught to dislike bitterness - they reject it instinctively. The opposite holds for sugars. Experiment after experiment finds the same thing: People are attracted to sugar from the moment they're born. These responses can be shaped by later learning, but they remain at the core of human behavior.

Sweetness in humans' futureAnyone who decides they want to reduce their sugar consumption is up against millions of years of evolutionary pressure to find and consume it. People in the developed world now live in an environment where society produces more sweet, refined sugars than can possibly be eaten.

There is a destructive mismatch between the evolved drive to consume sugar, current access to it and the human body's responses to it. In a way, we are victims of our own success.

The attraction to sweetness is so relentless that it has been called an addiction comparable to nicotine dependence - itself notoriously difficult to overcome.

It is worse than that. From a physiological standpoint, nicotine is an unwanted outsider to our bodies. People desire it because it plays tricks on the brain. In contrast, the desire for sugar has been in place and genetically encoded for eons because it provided fundamental fitness advantages, the ultimate evolutionary currency.

Sugar isn't tricking you; you are responding precisely as programmed by natural selection.

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Why do we love sugar so much? Here is a genetic connection to your sweet addiction - Economic Times

On November 24, 2021, scientists in South Africa revealed that they had discovered a worrying new variant of SARS-CoV-2.

They reported that the variant was spreading very rapidly in southern Africa and contained a large number of unusual mutations likely to make the virus more infectious than previous variants.

Within days of the scientists announcement, the World Health Organization (WHO) declared that the new variant, called Omicron, was a variant of concern.

Confirming the scientists early fears, by early January 2022, Omicron was driving an unprecedented surge in cases worldwide.

Many of the mutations that health experts identified in Omicron are rare among previously sequenced variants of the virus.

This presents a puzzle for scientists because there are no known intermediate variants to reveal how Omicron evolved. It is almost as if the new variant appeared out of nowhere.

There are three alternative theories for the origin of Omicron:

The second theory is the most popular among virologists and epidemiologists.

However, some experts have argued that other viruses, such as the influenza virus, tend to become less infectious over time in individuals with compromised immune systems.

They cite evidence that while such viruses evolve adaptations to their hosts immune system, they accumulate other mutations that make them less able to cause infections in other people.

However, Omicron appears to be more infectious than all previously known variants.

Researchers at the Chinese Academy of Sciences in Beijing have now found evidence that Omicron may have evolved its large collection of unusual mutations in mice.

They believe that an earlier variant, from the lineage known as B.1.1, jumped from a human into a mouse in mid-2020. Over time, it evolved a range of adaptations to its new host before causing an infection in another human in late 2021.

They identified 45 point mutations in the RNA of Omicron that they propose occurred after the variant split from its last known common ancestor in humans.

Point mutations are substitutions of single chemical letters, known as bases, in the four-letter genetic code.

Past research suggests RNA viruses tend to pick up more mutations in particular bases, according to which animal host they are replicating inside.

Using this knowledge, the authors of the new paper have previously identified the mutation signature of different animal hosts of SARS-CoV-2.

Their new study found that the relative frequency of the new point mutations in Omicron is characteristic of evolution in a mouse host rather than a human host.

They discovered that the mutation signature of Omicron is different from several variants known to have evolved in humans, including three variants isolated from patients with chronic COVID-19.

The scientists also found that several mutations in Omicrons spike protein, which SARS-CoV-2 uses to cause infection in host cells, help the virus bind more tightly to its target receptor in mice.

They have published their findings in the Journal of Genetics and Genomics.

In the paper, they conclude:

Collectively, our results suggest that the progenitor of Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host, then jumped back into humans, indicating an inter-species evolutionary trajectory for the Omicron outbreak.

Biologist Matt Ridley, author of Viral: The Search for the Origin of COVID-19, responded to the study on Twitter:

Looks like Omicron developed from a human variant in a mouse. The question is: what mice and where? House mice in homes? Or lab mice in labs?

We believe that Omicron likely evolved in a wild mouse population, the senior author of the study, Wenfeng Qian, Ph.D., told Medical News Today.

He said that mutations in the spike protein of Omicron significantly overlapped with mutations in SARS-CoV-2 viruses that have adapted to a mouse host.

However, 18 out of a total of 25 mutations in the Omicron spike were not present in any of the SARS-CoV-2 viruses they studied that were adapted to lab mice.

In addition, he pointed out that Omicron appears to have diverged from the B.1.1 lineage, with which it shares seven mutations.

It is implausible that a lab will use a B.1.1 variant for their mouse adaptation experiments, he commented. Instead, he said they would most likely use a strain of SARS-CoV-2 that researchers sequenced at the start of the pandemic, known as Wuhan-Hu-1.

Evolutionary biologist Mike Worobey, Ph.D., of the University of Arizona in Tucson, said the most plausible theory remained that Omicron evolved in an immune-compromised patient with a protracted [SARS-CoV-2] infection.

I think their approach is really interesting, but I still think it is more likely that the unusual array of mutations in Omicron occurred in a chronically human [with the infection], he told MNT.

For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.

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COVID-19: Did Omicron evolve in mice? - Medical News Today

On Wednesday, January 26 from 12:00 12:45pm, Marty Soehnlen, PhD, MPH, PHLD(ABB), and Heather Blankenship, PhD, will provide a presentation on the Omicron variant's concerning rise in Michigan, how whole genome testing is performed, impacts upon diagnostic tests, current data trends, and impacts upon therapies.

Doctor Soehnlen is the Director of Infectious Disease at the Michigan Department of Health and Human Services, Bureau of Laboratories. She began her laboratory career at Ohio State University where she received a BS in Medical Technology followed by an MPH is Hospital and Molecular Epidemiology with a sub-specialization in public health genetics. Doctor Soehnlen went on to the Centers for Disease Control and Prevention as an APHL/CDC Class XII Emerging Infectious Diseases Fellow in the Rabies group before obtaining a PhD in Pathobiology from Penn State University. She spent 4 years in Landstuhl, Germany with the US Army Public Health Command Region in Europe. She also directs three local health department labs and one small commercial lab.

Doctor Blankenship is Section Manager of Bioinformatics and Sequencing at the Michigan Department of Health and Human Services, Bureau of Laboratories. She received her BS in Biology from George Mason University and her PhD from Michigan State University. She gained expertise for her career through study of human and prokaryotic genetics. Her post graduate studies focused on molecular genetics, epidemiology, biotechnology, and bioinformatics.

Approved for .75AMA PRA Category 1 Credit(s)

Please visit our website for more information or to register>>

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Grand Rounds: Omicron The Next Variant of Concern and Responses in the COVID Pandemic Efforts - Michigan State Medical Society

Work type: Full-timeDepartment: Li Ka Shing Faculty of Medicine (20000)Categories: Academic-related Staff

Assistant Research Officer (holding the functional title of Bioinformatic Scientist II) in the LKS Faculty of Medicine (Ref.: 511404)(to commence as soon as possible, on a two-year fixed-term basis with contract-end gratuity and University contribution to a retirement benefits scheme, totalling up to 10% of basic salary, with the possibility of renewal)

Applicants should possess a Ph.D. degree in Genetics, Molecular Biology or Computational Biology/Bioinformatics. Experience with next-generation sequencing data analysis, proficiency in Python, R and Linux scripting, including evidence of the use of source code management repositories are essential. Applicants should have solid knowledge of molecular and human genetics, and demonstrated ability to effectively communicate scientific results in presentations and publications.

The appointee will work with a multi-disciplinary team including clinicians and scientists to study undiagnosed disorders and cancers through analysis of whole genome sequencing data coupled with clinical information as part of the Hong Kong Genome Project Partnering Centre based at The University of Hong Kong and Queen Mary Hospital. Responsibilities include to implement bioinformatics pipelines for the processing and management of genomics data, design workflow for the prioritisation and validation of genomic variants of potential significance, provide advanced scientific support for the interpretation of potential variants of significance in relation to the disease of individual patients. Enquiries about the duties of the post should be sent to Professor Suet Yi Leung at suetyi@hku.hk.

A highly competitive salary commensurate with qualifications and experience will be offered, in addition to annual leave and medical benefits.

The University only accepts online application for the above post. Applicants should apply online and upload an up-to-date C.V. Review of applications will start from January 19, 2022 and continue untilJanuary 31, 2022, or until the post is filled, whichever is earlier.

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Assistant Research Officer, Li Ka Shing Faculty of Medicine job with THE UNIVERSITY OF HONG KONG | 276845 - Times Higher Education (THE)

The spike protein of the coronavirus, or SARS-CoV-2, binds to a receptor on the host cells, called ACE2, which allows the virus to enter the cells and infect it. Binding is the first step for infection, and several mutations in previous variants of concern have been shown to be important for increasing the spike's binding to human ACE2.

We use a fully quantum mechanical model to theoretically assess how different mutations in the spike can contribute to its increased, or decreased, binding strength to human ACE2, Momeni said. The modeling shows that Omicron binds to receptor proteins stronger than the currently dominant Delta variant.

In addition to Momeni, Boston College Professor of Biology Welkin Johnson and post-doctoral researcher Marco Zaccaria, Luigi Genovese of French CEA - University of Grenoble Alpes, and Professor Michael Farzan of the Scripps Research Institute, contributed to the report"Investigating the mutational landscape of the SARS-CoV-2 Omicron variant viaab initioquantum mechanical modeling,which is available at the pre-print host site bioRxiv.

We find that Omicron has not reached its full potential to bind human host cells, Momeni said. We identify mutations that can strengthen the virus affinity for the human cell, which could increase infectivity and evasion of antibodies. He cautioned that increased infectivity is only one important aspect in variants of concern; it is also important to monitor the severity of symptoms and the ability of the variant to evade antibodies and vaccines.

While the study found that Omicrons spike proteins bind better than the Delta variant to the human ACE2 receptor, not all mutations in the spike proteins targeting systemknown as a receptor binding domainare beneficial for binding, which suggests factors other than binding may also be involved in determining how the variant evolves.

One possible explanation is that the variant has acquired mutations to evade host antibodies, Momeni said. Such mutations can be detrimental to its binding to the host receptor and were followed by additional compensatory mutations to recover, or even improve, its receptor binding.

Momeni said the team was surprised to see a range of mutationssome beneficial, some neutral, and some detrimentalto hACE2 binding. He said the teams next steps are to experimentally validate the predictions of the model.

The teams findings on Omicron build upon a prior analysis of the Wuhan and Delta variants by the team. There, modeling found that E484 was actually a weak link in the original Wuhan strain, but it has evolved through mutation to better bind to human host cells and to evade some antibodies, Momeni said. Additionally, the team found that the Wuhan strain bindingto ACE2 in bats was more optimized than the human counterpart. The team predicted further E484K mutation added to the Delta variant would produce a future variant of concern.

Ed Hayward | University Communications | December 2021

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Predicting the future of COVID - Boston College Chronicle