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[from left to right, Ozlem Tureci, Kizzmekia Corbett, Katalin Kariko and Emma Walmsley. Sources: Wikipedia.com, Harvard.com, Britannica.com, fortune.com]

On March 20222, we mentioned Women in History Month celebrating and acknowledging womens contributions to human history. In celebration of this significant month and before it officially comes to an end, we gathered a few women who changed the face of Biotech and led us in the fight against COVID-19:

Ozlem Tureci is the Co-Founder and Chief Medical Officer of BioNTech, a German biotech company that developed the worlds first authorized mRNA vaccine for preventing COVID-19. She led Project Lightspeed, BioNTechs successful and historic project for developing the vaccine, which was completed in less than one year. Tureci and her husband, Ugur Sahin, co-founder and CEO of BioNTech, make an inspiring Power Couple in the pharma industry.

Tureci is a woman of many specialties as she is a physician, Immunologist, cancer researcher, and entrepreneur. Turecis current focus is on cancer research; she led the efforts in the discovery of cancer antigens and the development of individualized as well as off-the-shelf mRNA vaccines. She aims to use personalized approaches to help the patients immune system defend itself against cancer. This is a unique and more effective approach when dealing with cancer treatment methods. In addition to her ongoing research and initiatives, Tureci is a professor at the University Medical Center Mainz and Helmholtz Institute for Translational Oncology Mainz (HI-TRON) for personalized immunotherapy.

Ozlem Tureci is an inspirational business and biotech leader. Her dedication, love of science, motivation, and brilliance contributed to the creation of this list of accomplishments that we are sure will only continue to grow.

Katalin Kariko is a Hungarian American biochemist known as one of the heroes of the development of the Covid-19 vaccine. Her work and development of In Vitro-Transcribed mRNA Therapies laid the groundwork for research for the vaccines developed by the Pfizer-BioNTech partnership with Moderna.

Karikos ideas in mRNA development were considered to be unorthodox for many years and were not always understood or approved by surrounding scientists. Her biggest challenge was to receive the grants necessary to fund her research. Kariko did not give up and through her persistence she prevailed which led her to life-changing discoveries, helping the world conquer the covid-19 pandemic.

Kariko received multiple well-deserved awards as acknowledgment for her breakthroughs and life-changing research. Some of the awards include the Breakthrough Prize in life sciences and Glamour Women of The Year. Many also argue that she deserves a Nobel Peace Prize we definitely agree!

Dr. Kizzmekia Corbett is an American viral immunologist and assistant professor of Immunology and infectious diseases at Harvard University. She played an integral part in the creation and development of Modernas COVID-19 vaccine. Dr. Corbett was appointed to the Vaccine Research Center (VRC) at the NIAID NIH institute and was the scientific lead of the VCRs Covid-19 Team.

Dr. Corbett is now leading her private lab at Harvard University, called the T.H Chan School of Public Healths department of immunology and infectious diseases. In her lab, Dr. Corbett focuses on viral immunology that can assist in pandemic preparedness and the development of universal vaccines.

Dr. Corbett was highlighted in February 2021 in the Times Time100 Next list, under the categoryInnovators. Her passion and humane approaches are disclosed to all. Corbett feels strongly about a family work environment and believes that each person is a crucial and equal part of the system.

Last but not least, Emma Walmsley is the CEO of GlaxoSmithKline (GSK), a British multinational pharmaceutical company, and is considered the first woman ever to run a major pharmaceutical company. GSK collaborated with Sanofi, a French multinational healthcare company, to contribute to the worldwide effort in developing the Covid-19 vaccine.

Since taking over the role of CEO at GSK, Walmsley has led a global reconstruction program that aims to save the company significant amounts of money. The program shifted the companys focus to four main areas of research and development: respiratory, HIV, Oncology, and immune inflammation.

Walmsley presented a courageous and strong approach when joining GSK, not afraid to take charge and shake things up. Thanks to Walmsley, GSK is also one of the prominent Biotech companies to take an open stand against the injustices currently occurring in Ukraine.

These magnificent women didnt fight alone in the war against Covid-19. Many other women, who were not mentioned in this list, contributed to the causes, changing the fields of Science and Biotech as we knew them.

This article is written by Katherine Gray.

Katherine Gray is a Boston-based Journalist who specializes in Health Care. Also active at The Activist Lab, Katherine often deals with topics such as social injustice in the fields of Health and Science.

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Unforgettable: The women that changed Biotech - Euro Weekly News

Immunology

Dr. Catherine Kibirige develops HIV tests to advance vaccine and cure research – Afro American

March 29, 2022 medical

By Megan Sayles, AFRO Business Writer, Report for America Corps Member msayles@afrocom

Dr. Catherine Kibirige was a teenager when she decided her career would center on HIV research.

Her parents were natives of Uganda, but she was born in Kenya after they were exiled during the Ugandan Civil War. Eventually, her father got a job in London as an engineer, and he sent for Kibirige and her sister to come join him.

While in secondary school, Kibirige learned that Uganda had been severely hit by HIV and AIDS. The first cases of HIV in Africa were recorded and characterized in the Rakai District, a community in the central region of Uganda.

Wed just come out of a civil war, so it was very devastating. On top of all the issues with the civil war, thered been famine, thered been desolation and then we had HIV, said Kibirige. It really had a huge impact on us as a nation and I lost a lot of close relatives. I knew I wanted to be involved in HIV research.

After college, Kibirige traveled to Uganda to volunteer with the Ministry of Health and work in the Rakai Health Sciences Program, a collaboration between researchers at Makerere, Columbia, Johns Hopkins Universities and the Division of Intramural Research at the National Institute of Allergy and Infectious Diseases.

She was offered a job on a study of HIV, AIDS and related STDs just a few months after she started volunteering. Two years into the position, she was sponsored to come to the United States to obtain her doctorate of philosophy from the Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health.

Her first post-doctoral fellowship was with the U.S. Militarys HIV Research Program, which at the time was administering a vaccine trial in Thailand. The trial was using an assay, a lab test used to find and measure the amount of a specific substance, that did not detect all of the circulating HIV subtypes.

Kibirige redeveloped the assay so it would be ultra-sensitive and better cover HIV subtypes and variants.

She then went back to Johns Hopkins University for a second post-doctoral fellowship to further optimize the assays and broaden their utility.

Now, Kibirige is expanding on her work as a research associate at Imperial College London in the Human Immunology Laboratory. She maintains a provisional patent on the assay she developed.

Her hope is to commercialize her assay in Uganda to help Africa move away from donor dependence.

We need to get to the point now where were actually making our own reagents, doing our own vaccine research and not having to import everything. One of the things that really stood out to me when I worked for Rakai is everything is imported, even the paper towels and [cotton] swabs.

In Uganda those with HIV face significant barriers to accessing treatment monitoring, leading to a surge in drug resistance. District hospitals have to send blood samples to the national HIV testing lab in Kampala, the countrys capital. Results can get lost, and even if they dont, they take months to get back to the district hospitals.

Currently, Kibirige is in negotiations to transfer her assays manufacturing process to Uganda. She intends for her assay to be a low-cost, ambient-temperature and prolonged-shelf life alternative to viral load testing.

Shes also in the early stages of establishing a startup that will streamline the process of transporting the assays for use in resource-limited areas in Uganda.

I just want to encourage women- especially women in science and technology- to really pursue their dreams, stick to whatever vision they have and just be open to exploring different kinds of avenues, said Dr. Kibirige.

Never give up.

Help us Continue to tell OUR Story and join the AFRO family as a member subscribers are now members! Joinhere!

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Dr. Catherine Kibirige develops HIV tests to advance vaccine and cure research - Afro American

Immunology

Manitobans ‘living in the dark’ with COVID risk, experts fear – Winnipeg Free Press

March 29, 2022 medical

Manitobans and their health-care system are vulnerable to a sneak attack from another devastating COVID-19 wave after the province cut back on virus data collection and reporting, experts warn.

The government has ditched weekday updates of its coronavirus dashboard, which contained case counts, the positivity rate, hospitalizations and deaths, in favour of weekly epidemiology reports.

As the government lifted all of its restrictions earlier this month, chief provincial public health officer Dr. Brent Roussin encouraged Manitobans to assess their own personal risk going forward.

But Manitobans are unable to do that without transparency from the government amid limited testing and a lack of contact tracing, said Dr. Julie Lajoie, a research associate working in virology and immunology at the University of Manitoba.

"We are living in the dark in terms of what is happening with COVID in Manitoba," said Lajoie.

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Based on upward trends in Quebec and Ontario and anecdotal evidence, she suspects infections are rising in Manitoba and is expecting a fifth wave to hit the province.

"I think there is no way were not going to see it," she said. "It is coming or it is already on us."

However, it is difficult to know the true scale of COVID in Manitoba and to predict a new wave without reliable data, she said, adding case counts are being underreported because access to PCR tests is limited and rapid test results are not tallied up.

A lag means hospitalization and municipal wastewater data are not as useful, she said.

Wastewater trends up to March 13 were released Monday by the Public Health Agency of Canada. The province insists it cannot release that data because it is "owned, collected and posted by the National Microbiology Lab."

Lajoie said one of the main indicators for Manitoba is whats happening in other provinces. Quebec appears to be heading into a sixth wave, and Ontarios positivity rate has jumped to its highest level since January, when the Omicron variants wave was peaking.

Both provinces reported a decrease in intensive-care admissions Monday.

"We can only rely on whats happening around us," said Lajoie. "We have to take into consideration that thats happening in Manitoba, as well."

Without data that is properly collected and analyzed, it is impossible to identify trends and intervene before it is too late, warned Winnipeg critical-care physician Dr. Doug Eyolfson.

"Its dangerous. The health system cant react to a situation if it doesnt know what the trends are," said Eyolfson, a former Liberal member of Parliament. "The only indicator we have right now is hospitalization rates, and thats a lagging indicator."

MIKAELA MACKENZIE / FREE PRESS FILES

"Its dangerous. The health system cant react to a situation if it doesnt know what the trends are," said Doug Eyolfson.

In a COVID recovery plan published March 15 the day restrictions were lifted Shared Health said it was preparing for a potential increase in virus transmission and hospital admissions.

As of last Thursday, eight of Winnipegs 39 long-term care homes had active COVID outbreaks, the Winnipeg Regional Health Authoritys website stated Monday.

Eyolfson, who works at Grace Hospital, said he is still seeing COVID cases, but the numbers arent as high as they were during the previous wave.

He said the provinces decision to ditch its vaccine mandate for non-essential businesses March 1 and its mask mandate for indoor public places March 15 was "premature."

"Im seeing less and less mask use everywhere I go now," he said." The phrase, living with the virus sounds good to say, but, unfortunately, people are still dying with the virus."

MIKAELA MACKENZIE / FREE PRESS FILES

Health Minister Audrey Gordon defended the governments data collection and reporting methods, insisting the province is providing sufficient information and will provide specific data requested by media.

She said the province continues to see a "downward trend," with eight of 19 intensive-care unit cases "active" as of Monday.

The government is making rapid antigen tests available at public places such as libraries and grocery stores, and people who receive a positive test result should call their physician or Health Links for information, she said.

"I dont think we have misled Manitobans in that we have stated that the new cases are, at times, underreported because individuals who are, like myself, triple-vaccinated, if they test positive their symptoms might be mild," Gordon said while visiting a new ambulance station in Portage la Prairie.

She urged people to stay home if they feel ill.

"What Im hearing is that most of the cases are mild to moderate symptoms and individuals are able to manage those symptoms very safely at home and with the care of their health-care provider," said Gordon.

Manitobas virtual COVID outpatient program has saved "many, many hospital days" by helping people to manage their symptoms at home, she said.

NDP health critic Uzoma Asagwara said Manitobans need access to "clear and transparent public health data" to help them make informed decisions about staying safe.

"With hospitals preparing for a surge in cases and public-health measures removed, right now seems like a bad time to leave families in the dark. The PCs should be sharing more info with Manitobans, not less," said Asagwara.

Liberal Leader Dougald Lamont claims the province hasnt learned from past mistakes.

"Its scary, because the Stefanson PCs actually seem to be going out of their way to be as unprepared as possible, making another wave of COVID more likely," he said. "The new Omicron (subvariant, known as BA.2) is even more infectious than the last. We need easy-to-reach PCR testing across the province, contact tracing, wastewater testing and reporting, daily updates, free masks, and vaccines and boosters need to be readily available for everyone. This would actually blunt the next wave. Instead, were flying blind."

Manitoba can "live with the virus" and avoid shutting down sectors by keeping precautions such as a mask mandate for indoor public places, improved ventilation in schools and daycares, and a mandatory self-isolation period for people who test positive, said Lajoie.

These are things that can help to reduce the spread of the virus, ease pressure on the health-care system and prevent cases of long COVID, she said.

"Its simple action and it will make a really big difference in the long run," she said. "Were all tired of COVID, but COVID is not tired of us. We still need to be careful."

Dr. Nazeem Muhajarine, a community health and epidemiology professor at the University of Saskatchewan, said the governments approach is not a good way to manage the pandemic.

"We are really flying blind these days without regular reporting and detailed reporting of COVID-19 numbers," said Muhajarine. "How could we assess our own risk without data given or shown to us? Its a no-win situation."

Muhajarine is not convinced COVID-19 has become endemic, as hospitalization rates are higher than expected and the more infectious Omicron strain circulates in the community.

Manitobans have been encouraged to get three doses of a COVID vaccine to protect themselves against Omicron and any future variants that are highly contagious.

"(Two) is still good to prevent severe infection, but we know against Omicron that a third dose is really needed," Lajoie said.

As of Monday, 44.7 per cent of eligible Manitobans had received three shots.

So far, only people 12 and older with weakened immune systems are being encouraged to get a fourth dose.

With files from Danielle Da Silva

chris.kitching@freepres.mb.ca

Twitter: @chriskitching

Immunology

Why the UK cant rely on boosters to get through each new wave of Covid – The Guardian

March 29, 2022 medical

This time in 2020, we watched with horror as the realities of the pandemic and its death toll unfurled. Most hardly dared imagine that effective vaccines might appear in a fraction of the time taken for previous efforts, effectively stemming the pandemic tide.

But despite the success of the vaccines in greatly reducing the odds of hospitalisation or death, viral evolution had plenty more to throw at us. The onslaught of highly immune-evasive variants was, for most of us in immunology and virology, unforeseen. Wed come to think of the coronavirus family as being rather more stable less error-prone in terms of mutations than many viruses. And we had never before had to roll out relatively new ways of developing vaccines, involving mRNA or recombinant adenoviruses, at this scale and in the heat of battle.

Having started out brilliantly, the real-life state of play today is self-evidently suboptimal. The vaccines rapidly induce hugely high levels of protective, neutralising antibodies in most people, but these levels wane within months of each sequential dose. Meanwhile, Omicron and the subvariant BA.2 have managed to mutate almost every amino acid residue targeted by protective antibodies, escaping protection. And so you have the unhappy equilibrium currently endured by the UK: more than 300,000 new cases a day, as of late last week, and a continuing caseload of more than 3 million, with hospital admissions and excess deaths holding steady at a new high setpoint. All this despite one of the highest vaccination rates in the world.

We are living in a precarious truce imposed through frequent mRNA boosters to keep the viral caseload manageable. But there are signs this isnt sustainable, and that a strategy simply consisting of boosters in perpetuity may not be fit for purpose. Recent case surges in Hong Kong, Denmark and Scotland emphasise the fragility of that balance. And new evidence from the past two years suggests that encounters with different variants of Covid or different vaccine types can alter the effectiveness of later jabs in surprising ways an effect called immune imprinting. This raises the possibility that booster performance could be even less predictable and effective in the future.

Sars-CoV-2 began as a single variant, which we term the Wuhan strain. But we now inhabit a world where no two people share precisely the same exposure history: we have never been infected, or were asymptomatically, mildly or severely infected during any or a combination of the Wuhan to Alpha, Delta, Omicron or BA.2 waves, and weve all had somewhere from zero to four doses of diverse vaccines. The combination of these exposures gives each of us a unique immune memory repertoire.

Imagine a huge jar of pills of different colours, each especially good for responding to a given present or future variant. Someone whose experience has been an Alpha infection plus three doses of Pfizer may have brilliantly built up lots of green pills at the expense of others. But this is less good for you if the next variant mainly needs yellow pills. It turns out the order and type of exposure can affect how our immune system responds later on.

In a recent paper reported in the journal Science, we compared protective immunity between people infected in the first wave with the original strain and in the second wave with the Alpha variant. In second wave-infected people, encounters with an Alpha infection plus two vaccine doses gave lower protective (known as neutralising) antibody responses against the Wuhan and Beta variant, yet higher responses against Delta. Given the number of vaccines and strains, these interactions are unpredictable, but will shape how our immunity holds for future waves. It needs more investigation.

These are complex problems demanding careful research, long-term planning, trials and even some intelligent crystal ball-gazing. We must evaluate many approaches. Some places have announced a fourth dose rollout for first generation Pfizer vaccines (which cross-neutralises recent variants, but very suboptimally); some vaccine makers have pivoted to targeting the Omicron spike; others are working on polyvalent vaccines to include several different versions of spike, or clever structural approaches to target those parts of spike that would be the same across all past and future variants, and maybe even across those coronaviruses still awaiting crossover from bats and pangolins.

This latter approach is exciting and the subject of recent efforts across many teams, including research trials through the US National Institutes of Health and at Cambridge University. There are also advanced programmes considering intranasal nose vaccination to achieve local mucosal immunity, increasing the chances of blocking transmission at that site altogether, and vaccine platforms that could be much more durable.

The take-home message is that the pandemic is very much with us and evolving dynamically, with a long, bumpy road ahead. The option to sleepwalk through this, taking automatic-pilot choices based on what was good enough in the first wave is one we adopt at our peril. We must look at options besides simply boosting through every successive wave. At a time when the US has cut future vaccine research funding, and the UK also needs to maintain its momentum, this should be an urgent priority.

Danny Altmann is a professor of immunology at Imperial College London, who has contributed advice to the Cabinet Office, APPG on long Covid, and the EU

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Why the UK cant rely on boosters to get through each new wave of Covid - The Guardian

Cell Biology

InGeneron Publishes Overview on Current State and Potential of Regenerative Cell Therapy in Orthopedics – Yahoo Finance

January 25, 2022 medical

Concise review outlines key concepts behind using a patients own regenerative cells for point-of-care treatment of orthopedic indications and the advantages of this approach compared with other methods.

HOUSTON, January 24, 2022--(BUSINESS WIRE)--InGeneron, Inc., a clinical stage biotechnology company, announced the publication of a succinct scientific review of regenerative cell therapy, commonly called "stem cell therapy", to treat orthopedic indications. This newly released paper, titled "Why and how to use the bodys own stem cells for regeneration in musculoskeletal disorders: a primer", was published in the Journal of Orthopaedic Surgery and Research (J Orthop Surg Res 17, 36 (2022): https://doi.org/10.1186/s13018-022-02918-8). The publication provides an approachable overview of stem cell biology and clarifies common misconceptions about adipose-derived regenerative cells (ADRCs) including vascular-associated pluripotent stem cells (vaPS cells). The authors emphasize the ability of therapies using ADRCs to readily fit into modern orthopedic treatment concepts and reference InGenerons proprietary cell therapy platform, currently under evaluation in ongoing FDA-approved trials.

Summarizing 20 years of both basic and clinical research, the review aims to provide a straightforward look at the current state of orthopedic regenerative cell therapies and clarifies the role of different regenerative cells, such as vaPS cells, in tissue regeneration. The publication highlights the advantages of InGenerons therapeutic approach utilizing ADRCs to develop point-of-care therapies compared to other types of "stem cell therapy", including techniques requiring cells to be cultured in a lab. Dr. Eckhard Alt, Director of Stem Cell Research at Tulane University (New Orleans, LA, USA), Executive Chairman of InGeneron and co-author of the paper explains: "Using unmodified, uncultured, autologous cells allows for true point-of-care treatment, which can be performed within a short time on the same day in an outpatient facility. Culturing and modifying cells before treatment increases the complexity and cost for patients and physicians and also increases the possibility for contamination of the cells and other health concerns, such as autoimmune rejection, that are not an issue when using ADRCs."

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Pointing out another advantage of InGenerons therapeutic approach, Dr. Christoph Schmitz, Head of the Department of Anatomy II at Ludwig-Maximilians University of Munich (Munich, Germany), Advisory Medical Director of InGeneron and co-author of the paper adds, "We realized early on that stem cells were important but that they benefitted from other cells contained in ADRCs such as progenitor cells, pericytes, endothelial cells and fibroblasts, which we collect from patients adipose tissue along with their stem cells. All of these cell types play an essential role in tissue regeneration and work synergistically, each affecting the other to promote healing in specific ways that we are still working to fully understand. Therapies that isolate stem cells for culturing in the lab lack these other cell types."

The publication concludes that utilizing ADRCs offers the most attractive therapeutic approach for providing safe and effective treatments, which can be integrated into the modern orthopedic clinical paradigm.

Building on the insights obtained from years of research studying regenerative cells, InGeneron is currently conducting three actively enrolling FDA-approved clinical trials to evaluate its cell therapy platform for the treatment of musculoskeletal indications such as partial-thickness rotator cuff tear, wrist osteoarthritis, and facet joint syndrome.

Publication Details

DOI: https://doi.org/10.1186/s13018-022-02918-8

Citation: Furia, J.P., Lundeen, M.A., Hurd, J.L. et al. Why and how to use the body's own stem cells for regeneration in musculoskeletal disorders: a primer. J Orthop Surg Res 17, 36 (2022).

About the Transpose RT System and Current Clinical Trials

InGenerons Transpose RT cell therapy platform consists of a processing unit, a set of disposables, and Matrase, a proprietary enzyme mixture. The platform allows the isolation of regenerative cells from the patients' own adipose tissue at point-of-care in less than 90 minutes for same-day treatment. The cells are re-administered into the patients damaged tissue by injection under ultrasound or fluoroscopic guidance.

The Transpose RT System is being investigated in several FDA-approved clinical trials and is currently available in the U.S. for research use only. More information on InGenerons actively enrolling clinical trials can be found at http://www.clinicaltrials.gov under the identifiers NCT03752827, NCT03513731, and NCT03503305.

About InGeneron

InGeneron is a clinical-stage biotechnology company developing novel, safe, and evidence-based cell therapies. We are setting new therapeutic standards by enabling minimally invasive treatments that unlock the healing potential of each patients own regenerative cells processed at the point of care for same-day treatment. We currently focus on helping patients impacted by orthopedic conditions and are conducting several clinical trials to validate our technology as a disease-modifying treatment. Based on more than 20 years of research, InGeneron is dedicated to developing therapies supported by clinical evidence and approved by the FDA.

http://www.ingeneron.com

View source version on businesswire.com: https://www.businesswire.com/news/home/20220124005479/en/

Contacts

InGeneron, Inc. Eckhard Alt, MD, PhDExecutive Chairman of InGeneron+1 (713) 440 9900press@ingeneron.com

Media Inquiries Jon StoneStone Communications Consulting+1 (612) 475 5955jon@stonecommunications.net

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InGeneron Publishes Overview on Current State and Potential of Regenerative Cell Therapy in Orthopedics - Yahoo Finance

Cell Biology

Landing Therapeutic Genes Safely in the Human Genome Improving Gene and Cell Therapies – SciTechDaily

January 25, 2022 medical

By Wyss Institute for Biologically Inspired Engineering at HarvardJanuary 24, 2022

A collaborative research team at Harvards Wyss Institute and the ETH Zurich in Switzerland has identified genomic safe harbors (GSHs) in the tumultuous sea of human genome sequence to land therapeutic genes in. As part of their validation, they inserted a fluorescent GFP reporter gene into candidate GSHs and followed its expression over time. The GSHs could enable safer and longer-lasting expression of genes in future gene and cellular therapies. This illustration won the team the cover of the Cell Reports Methods issue the study is published in. Credit: Erik Aznauryan

Researchers at Harvards Wyss Institute, Harvard Medical School, and the ETH Zurich predict and validate genomic safe harbors for therapeutic genes, enabling safer, more efficient, and predictable gene and cell therapies.

Many future gene and cell therapies to treat diseases like cancer, rare genetic and other conditions could be enhanced in their efficacy, persistence, and predictability by so-called genomic safe harbors (GSHs). These are landing sites in the human genome able to safely accommodate new therapeutic genes without causing other, unintended changes in a cells genome that could pose a risk to patients.

However, finding GSHs with potential for clinical translation has been as difficult as finding a lunar landing site for a spacecraft which has to be in smooth and approachable territory, not too steep and surrounded by large hills or cliffs, provide good visibility, and enable a safe return. A GSH, similarly, needs to be accessible by genome editing technologies, free of physical obstacles like genes and other functional sequences, and allow high, stable, and safe expression of a landed therapeutic gene.

Thus far, only few candidate GSHs have been explored and they all come with certain caveats. Either they are located in genomic regions that are relatively dense with genes, which means that one or several of them could be compromised in their function by a therapeutic gene inserted in their vicinity, or they contain genes with roles in cancer development that could be inadvertently activated. In addition, candidate GSHs have not been analyzed for the presence of regulatory elements that, although not being genes themselves, can regulate the expression of genes from afar, nor whether inserted genes change global gene expression patterns in cells across the entire genome.

Now, a collaboration of researchers at Harvards Wyss Institute for Biologically Inspired Engineering, Harvard Medical School (HMS), and the ETH Zurich in Switzerland, has developed a computational approach to identify GSH sites with significantly higher potential for the safe insertion of therapeutic genes and their durable expression across many cell types. For two out of 2,000 predicted GSH sites, the team provided an in-depth validation with adoptive T cell therapies and in vivo gene therapies for skin diseases in mind. By engineering the identified GSH sites to carry a reporter gene in T cells, and a therapeutic gene in skin cells, respectively, they demonstrated safe and long-lasting expression of the newly introduced genes. The study is published in Cell Reports Methods.

While GSHs could be utilized as universal landing platforms for gene targeting, and thus expedite the clinical development of gene and cell therapies, so far no site of the human genome has been fully validated and all of them are only acceptable for research applications, said Wyss Core Faculty member George Church, Ph.D., a senior author on the study. This makes the collaborative approach that we took toward highly-validated GSHs an important step forward. Together with more effective targeted gene integration tools that we develop in the lab, these GSHs could empower a variety of future clinical translation efforts. Church is a leader of the Wyss Institutes Synthetic Biology Platform, and also the Robert Winthrop Professor of Genetics at HMS and Professor of Health Sciences and Technology at Harvard University and the Massachusetts Institute of Technology (MIT).

The researchers first set up a computational pipeline that allowed them to predict regions in the genome with potential for use as GSHs by harnessing the wealth of available sequencing data from human cell lines and tissues. In this step-by-step whole-genome scan we computationally excluded regions encoding proteins, including proteins that have been involved in the formation of tumors, and regions encoding certain types of RNAs with functions in gene expression and other cellular processes. We also eliminated regions that contain so-called enhancer elements, which activate the expression of genes, often from afar, and regions that comprise the centers and ends of chromosomes to avoid mistakes in the replication and segregation of chromosomes during cell division, said first-author Erik Aznauryan, Ph.D. This left us with around 2,000 candidate loci all to be further investigated for clinical and biotechnological purposes.

Aznauryan started the project as a graduate student with other members of Sai Reddys lab at ETH Zurichs Department of Biosystems Science and Engineering before he visited the Church lab as part of his graduate work, where he teamed up with Wyss Technology Development Fellow Denitsa Milanova, Ph.D. He since has joined Churchs group as a Postdoctoral Fellow. Reddy, senior and lead author of the collaborative study, is an Associate Professor of Systems and Synthetic Immunology at ETH Zurich and focuses on developing new methods in systems and synthetic biology to engineer immune cells for diverse research and clinical applications.

Out of the 2,000 identified GSH sites, the team randomly selected five and investigated them in common human cell lines by inserting reporter genes into each of them using a rapid and efficient CRISPR-Cas9-based genome editing strategy. Two of the GSH sites allowed particularly high expression of the inserted reporter gene in fact, significantly higher than expression levels achieved by the team with the same reporter gene engineered into two earlier-generation GSHs. Importantly, the reporter genes harbored by the two GSH sites did not upregulate any cancer-related genes, said Aznauryan. This also can become possible because regions in the genome distant from one another in the linear DNA sequence of chromosomes, but near in the three-dimensional genome, in which different regions of folded chromosomes touch each other, can become jointly affected when an additional gene is inserted.

To evaluate the two most compelling GSH sites in human cell types with interest for cell and gene therapies, the team investigated them in immune T cells and skin cells, respectively. T cells are used in a number of adoptive cell therapies for the treatment of cancer and autoimmune diseases that could be safer if the receptor-encoding gene was stably inserted into a GSH. Also, skin diseases caused by harmful mutations in genes controlling the function of cells in different skin layers could potentially be cured by insertion and long-term expression of a healthy copy of the mutated gene into a GSH of dividing skin cells that replenish those layers.

We introduced a fluorescent reporter gene into two new GSHs in primary human T cells obtained from blood, and a fully functional LAMB3 gene, an extracellular protein in the skin, into the same GSHs in primary human dermal fibroblasts, and observed long-lasting activity, said Milanova. While these GSHs are uniquely positioned to improve on levels and persistence of gene expression in parent and daughter cells for therapeutics, I am particularly excited about emerging gain-of-function cellular enhancements that could augment the normal function of cells and organs. The safety aspect is then of paramount importance. With an entrepreneurial team at the Wyss, Milanova is developing a platform for genetic rejuvenation and enhancements with a focus on skin rejuvenation.

An extensive sequencing analysis that we undertook in GSH-engineered primary human T cells clearly demonstrated that the insertion has minimal potential for causing tumor-promoting effects, which always is a main concern when genetically modifying cells for therapeutic use, said Reddy. The identification of multiple GSH sites, as we have done here, also supports the potential to build more advanced cellular therapies that use multiple transgenes to program sophisticated cellular responses, this is especially relevant in T cell engineering for cancer immunotherapy.

This collaborative interdisciplinary effort demonstrates the power of integrating computational approaches with genome engineering while maintaining a focus on clinical translation. The identification of GSHs in the human genome will greatly augment future developmental therapeutics efforts focused on the engineering of more effective and safer gene and cellular therapies, said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and Boston Childrens Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.

Reference: Discovery and validation of human genomic safe harbor sites for gene and cell therapies by Erik Aznauryan, Alexander Yermanos, Elvira Kinzina, Anna Devaux, Edo Kapetanovic, Denitsa Milanova, George M. Church and Sai T.Reddy, 14 January 2022, Cell Reports Methods.DOI: 10.1016/j.crmeth.2021.100154

Additional authors on the study are Alexander Yermanos, Ph.D, and Edo Kapetanovic, members of Reddys group; Anna Devaux at the University of Basel, Switzerland; and, Elvira Kinzina at the McGovern Institute for Brain Research at MIT. The study was supported by ETH Research Grants, the Helmut Horten Stiftung and Aging and Longevity-Related Research Fund at HMS, as well as a Genome Engineer Innovation Grant 2019 from Synthego to Aznauryan.

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Landing Therapeutic Genes Safely in the Human Genome Improving Gene and Cell Therapies - SciTechDaily

Cell Biology

Global Cloud Computing in Cell Biology, Genomics and Drug Development Market Scope 2021 Growth Rate and Major Players are Google Inc., Amazon Web…

January 25, 2022 medical

The current MarketsandResearch.biz research report focuses on the Global Cloud Computing in Cell Biology, Genomics and Drug Development Market growth rate from 2021 to 2027 and the elements that will drive the industrys development. The paper investigates past market performance, current growth factors, and anticipated emerging technologies. The report explores the industrys origins and future growth prospects, and noteworthy traders who have succeeded in this market.

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Pharmaceutical and Biotechnology Companies, Contract Research Organizations (CROs), Clinical Laboratories, Hospitals and Research Institutes, Others,

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Public Cloud, Private Cloud, Hybrid Cloud,

The global Cloud Computing in Cell Biology, Genomics and Drug Development market research discusses the following regions and countries:

North America (United States, Canada and Mexico), Europe (Germany, France, United Kingdom, Russia, Italy, and Rest of Europe), Asia-Pacific (China, Japan, Korea, India, Southeast Asia, and Australia), South America (Brazil, Argentina, Colombia, and Rest of South America), Middle East & Africa (Saudi Arabia, UAE, Egypt, South Africa, and Rest of Middle East & Africa)

In the global market, the companies which are covered:

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Global Cloud Computing in Cell Biology, Genomics and Drug Development Market Scope 2021 Growth Rate and Major Players are Google Inc., Amazon Web...

Cell Biology

Revealing the mysterious biology of a fundamental process: reproduction | Penn Today – Penn Today

January 25, 2022 medical

Reproduction is a complex process, requiring a huge variety of molecular and cellular interactions, many aspects of which remain a mystery to science.

Solving some of these mysteries drives the curiosity and research of P. Jeremy Wang, professor of developmental biology in the School of Veterinary Medicines Department of Biomedical Sciences. Wang also directs the Center for Animal Transgenesis and Germ Cell Research. For the last two decades, his lab has focused on understanding the process of meiosis, the special type of cell division that gives rise to germ cells: sperm and eggs.

Three recently published studies illuminate some of the diverse strands of the Wang labs research.

By whipping their tails, known as flagella, sperm propel themselves through the female reproductive tract. Interacting with and moving through the zona pellucida, the thick coating that shrouds eggs, is energetically demanding. That stage of fertilization is powered by the activity of a calcium ion channel formed by a protein complex known as CatSper.

In the journal Development, Wang and colleagues describe a newly identified component of CatSper, a protein called C2CD6. Wangs team found that inactivating C2CD6 did not affect females but rendered males sterile. Their sperm count is normal, their sperm look normal, but they werent able to produce pups, Wang says.

The proteins location in the flagellum suggested a possible role in sperm motility.

And, indeed, the team found that C2CD6-deficient sperm were unable to enter what's known as hyperactivation, where a ramping up in calcium channel signaling gives sperm the burst of energy required to penetrate the zona pellucida. The work underscores the essential nature of this component of the CatSper complex; C2CD6 is in fact so essential, Wang says, that it could facilitate a drug screening system to find a male contraceptive.

A lot of people have thought about targeting the CatSper complex for a contraceptive, Wang says. Knowing this component of the complex might help scientists test which compounds would effectively stop sperm from being able to fertilize an egg.

A second recent study, described in Biology of Reproduction, looks at the female side of the reproductive process, specifically, what happens when it goes awry. In studying the CCNB3 gene, located on the X chromosome and believed to function in meiosis, Wang and colleagues found that male mice lacking CCNB3 appeared normal. But females, while they could become pregnant, lost the pregnancy at an early stage.

Detailed analysis by Wang and his team uncovered why these miscarriages arise. They found that CCNB3mutations which occur in humans as wellnormally helps meiosis progress. When the gene is not functioning normally, eggs that should have only one set of chromosomes wind up with two sets. That means a fertilized egg, with a set contributed from a sperm, would wind up with three sets of chromosomes, a genetic scenario incompatible with life.

The finding has translational value, Wang says.

With personalized or precision medicine, if a woman gets their genome sequenced and knows they have this mutation, doctors could take their egg, add a functional version of CCNB3 to rescue the defect, and then perform in vitro fertilization and end up with a normal embryo.

A third publication returns to the bread and butter of Wangs research: the intricacies of meiosis. In the journal Cell Reports, Wang and his team uncovered a new way in which YTHDC2, an RNA-binding protein, operates during the cell division process.

Other research groups had previously studied this protein, conducting genetic knockout experiments, where the gene was fully inactivated, to show that it acted during the early stages of meiosis.

Wangs lab, however, employed a different technique whereby they could allow YTHDC2 to function until meiosis had already begun. By doing so, they found that the protein had a second role later in meiosis, acting to maintain whats known as the pachytene stage, the lengthiest meiosis stage, lasting six full days.

It looks like YTHDC2 is a master regulator, says Wang. It appears to bind to RNA and help degrade or silence transcripts that are not supposed to be there, helping the cell commit to meiosis and allow the process to progress. While no YTHDC2 mutations have been found in humans linked with infertility, Wang says, its just a matter of time.

Future work in the Wang lab will pick up where some of these findings left off, continuing to uncover the workings of these fundamental processes.

These studies were supported by the National Institutes of Health (grants HD069592, HD068157, HD038082, HD088571, GM108556, HD03185, HD069592, and GM118052), China Scholarship Council fellowship, Swiss National Science Foundation, National Key Research & Development Program of China, Howard Hughes Medical Institute, and Human Frontier Science Program.

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Revealing the mysterious biology of a fundamental process: reproduction | Penn Today - Penn Today

Cell Biology

Senior Specialist Technician job with KINGS COLLEGE LONDON | 278848 – Times Higher Education (THE)

January 25, 2022 medical

We are seeking high-quality technical support to work on different biology-related projects within the Biological Physics and Soft Matter (BPSM) research group in the Department of Physics. We are seeking a talented, organized, friendly person who can assist with the molecular and cell biology aspects of the research agenda, and be able to assist the work of several laboratories. We especially need someone who is gifted in molecular biology skills and has vast knowledge in the latest cloning methods, as well as having expertise on cell culture and cell transfection.

The position will be temporarily held at the Francis Crick Institute, although it will be managed by Kings College London, within the framework of the seconded laboratory that Prof Garcia-Manyes has established at the Francis Crick Institute, although it will also assist other groups within the BPSM group.

Within Kings, the position will be managed from the department of Physics, with belongs to the Faculty of Natural, Mathematical & Engineering Sciences (NMES). NMES comprises Chemistry, Engineering, Informatics, Mathematics, and Physics with all departments highly rated in research activities and a wide-ranging portfolio of taught and research programmes. Supporting our staff is important to us and we offer a range of provision including flexible working, caring support, training, and promotion opportunities.

The university is making significant investment in the Faculty and both student and staff numbers are growing. Our staff come from over 45 countries and around 56% of our students are from outside the UK.

Further details available at http://www.kcl.ac.uk/nms

The study of Physics at King's dates back to the foundation of the College in 1829. The Department is currently undergoing significant growth with substantial investment in new appointments, research infrastructure and laboratory space refurbishment. We offer a range of BSc (three-year) and MSci (four-year) undergraduate courses as well as MSc and PhD programmes.

Further information may be found at:http://www.kcl.ac.uk/physics

This post will be offered on an a fixed-term contract for 18 months, with the possibility of becoming permanent

This is a full-time post

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Senior Specialist Technician job with KINGS COLLEGE LONDON | 278848 - Times Higher Education (THE)

Cell Biology

Research Fellow, Neurodevelopment and Degeneration Lab job with NATIONAL UNIVERSITY OF SINGAPORE | 278305 – Times Higher Education (THE)

January 25, 2022 medical

Job Description

A Postdoctoral Fellow position is available for PhD holders with experience in neuroscience and stem cell biology research. The successful candidate will manage and execute research projects (including design, conduct, collection of experiments and data analyses) and provide support to the Principal Investigator and his team.

Qualifications

Candidates should possess strong background and working knowledge of molecular biology, cell biology and biochemical techniques such as cell culture, cloning, real-time PCR, western blotting, immunoprecipitation, immunofluorescence-based microscopy. Candidates with familiarity in the handling of viral vectors and stem cells are highly desirable. Experience in animal handling, breeding and behavioural studies would be an advantage.

Candidates are expected to be able to work both independently and in team-based projects, be able to effectively communicate in written and spoken English. Applications should include full curriculum vitae, publication list, information on years of experience in research and laboratory work, and names and contact information (email and telephone numbers) of 3 referees.

Please send applications to: Assistant Prof John Chua (email: phsjcje@nus.edu.sg).

Only shortlisted candidates will be contacted.

Additional Information

At NUS, the health and safety of our staff and students is one of our utmost priorities and COVID-vaccination supports our commitment to ensure the safety of our community and to make NUS as safe and welcoming as possible. Many of our roles require significant amount of physical interactions with student / staff / public members. Even for job roles that can be performed remotely, there will be instances where on-campus presence is required.

With effect from 15 January 2022, based on Singapores legal requirements, unvaccinated workers will not be able work at the NUS premises. As such, we regret to inform that job applicants need to be fully COVID-19 vaccinated for successful employment with NUS.

More Information

Location: Kent Ridge CampusOrganization: Yong Loo Lin School of MedicineDepartment : PhysiologyEmployee Referral Eligible: NoJob requisition ID : 11735

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Research Fellow, Neurodevelopment and Degeneration Lab job with NATIONAL UNIVERSITY OF SINGAPORE | 278305 - Times Higher Education (THE)