Genetics

Genetic ancestry linked to diabetes, heart failure and obesity among Native Hawaiians | Keck School of Medicine of USC – USC News

First-ever large-scale genetic study examining Hawaiian Polynesians and health risk is led by the Keck School of Medicine of USC

(Photo/iStock)

By Wayne Lewis

With advances in analyzing human DNA, some well-studied populations have benefited from insights about how their health is affected by their genetics. Others, however, have been left behind. Among them are people of Polynesian descent from Hawaii.

Although population studies of Native Hawaiians have shown a substantial increase in risk for obesity, type2 diabetes, heart disease and certain cancers compared to their neighbors of European and Asian descent, there has been little to no insight into how genetics contribute on top of environmental factors to influence these disparities.

In an attempt to begin rectifying that gap, a USC-led research team has conducted the first study to systematically investigate the genomes of Native Hawaiians and test the components for health risks associated with genetic ancestry. The findings, which appeared in the journal PLoS Genetics, show that, for example, Polynesian ancestry in Native Hawaiians is linked to increased risk of diabetes, heart failure and higher body-mass index, a measure of body fat.

(Charleston Chiang. USC Photo/Ricardo Carrasco III)

Native Hawaiians really have been understudied from a genetic perspective, said corresponding author Charleston Chiang, PhD, an assistant professor of preventive medicine at the Keck School of Medicine of USC and of quantitative and computational biology at USC Dornsife College. Health disparities are a major research emphasis at USC in general, and my team focuses on looking at the genetic component of health risk within geographically diverse populations.

Characterizing Hawaiian Polynesian genetics to understand health risk

Chiang and his colleagues correlated health data (from questionnaire, laboratory measurements, and hospital Medicare claims) and the genetics of 3,940 people who identify as Native Hawaiian from the Multiethnic Cohort Study, a joint project of USC and the University of Hawaii. The research team found that for each 10% increase in estimated Polynesian ancestry, there is on average an 11% increase in risk of heart failure, an 8.6% increase in risk of type2 diabetes and a 0.35 unit increase in body-mass index.

Further studies may be able to identify genetic variants and underlying biological factors specific to Polynesian populations, knowledge that could help reduce these health risks. Chiang also hopes to test a hypothesis outlining a combination of nature and nurture.

For example, its possible that Native Hawaiians had adapted to a traditional diet, and the introduction of the Western diet has led to all kinds of health problems, he said. Thats actually an interaction between their genetics and their environment.

There was a unique challenge for the studys authors to overcome: Researchers focusing on the genetics of people with roots in Europe, Africa and Asia are able to call upon publicly available genomic references for those populations. No such resource exists for Polynesian ancestry. Native Hawaiians are characterized by a mixture of Polynesian, Asian, European and African ancestry. Using the existing references from other populations to run two analyses, the scientists searched for known origins as reflected both across each participants entire genome and location by location along their chromosomes. The research team essentially constructed a genomic model for Polynesian ancestry among Native Hawaiians by identifying a subsample of roughly 150 participants with the least amount of external heritance.

Genomics cant define ethnicity, and biology is not destiny

As should be expected with research charting new territory in biomedical science, the studys authors urge that their findings be interpreted with care and clarity on a few fronts.

Chiang pointed out that race and ethnicity are socially constructed concepts, and distinct from the issues explored in this study that is how certain genes shared among a population contribute to specific health metrics and outcomes. Ethnicity instead is, and should be, defined by genealogical records or how a person self-identifies.

Geneticists should not try to quantize a persons ancestry and use that to define whether that person belongs to a particular ethnic group, he said. While we needed to quantify the proportion of Polynesian ancestry in order to perform our research, we do not want to give the impression that this is a way for people to define their membership in the community based on some arbitrary threshold.

Additionally, Chiang emphasized that the model for Polynesian heritance among Native Hawaiians does not necessarily apply perfectly to populations in other islands such as Samoa.

Perhaps most important, the links between genetics and health revealed in this study should not be construed to mean that being part of any particular population automatically relegates a person to poor health in and of itself.

Genetics is a window into understanding the biology behind these diseases, Chiang said. Genetics does not determine everything, and it doesnt necessarily even amount to the majority of the disparity in risk. I want people to know there are modifiable components to your lifestyle, such as a healthy diet and regular hula dancing, that will absolutely help.

About the studies

The studys co-first authors are Hanxiao Sun, a former masters student in Chiangs research group, and Meng Lin, a former postdoctoral researcher in the group. Other authors are Tsz Fung Chan, Bryan Dinh and Christopher Haiman of USC; Emily Russell and Ryan Minster of the University of Pittsburgh; Take Naseri of the Government of Samoas Ministry of Health; Muagututia Sefuiva Reupena of Lutia i Puava ae Mapu i Fagalele, a nongovernmental organization based in Samoa; Annette Lum-Jones, Lynne Wilkens and Loc Le Marchand of the University of Hawaii; the Samoan Obesity, Lifestyle, and Genetic Adaptations Study Group; and Iona Cheng of the University of California, San Francisco.

The study was supported by the National Cancer Institute (U01CA164973, P01CA168530) and the National Human Genome Research Institute (U01HG007397).

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Embryology

The 14-day limit should be extended to 28 days – BioNews

15 February 2021

MSc Bioethics and Society student, King's College London

The '14-day rule', initially proposed in 1979 in the USA, was first recommended in the UK by the Warnock Committee in 1984. It limits research on intact human embryos to 'prior to 14 days' gestation or the beginning of primitive streak formation' and is part of the Human Fertilisation and Embryology Acts of 1990 and 2008(HFE Acts).

This legislation has been successfully implemented in the UK, but also in several other countries (eg, Australia's Research Involving Human Embryos Act 2002). It is followed in jurisdictions without relevant laws or even guidelines. While researchers accepted the rule, and have been content to keep to it, many contend that it was simply an arbitrary time limit that was chosen as a compromise to authorise any research at a time when pro-life views were strong. While originally it was a barrier that could not be breached for practical reasons, recent research on human and non-human primate embryos suggest that we now have methods to culture intact human embryos beyond 14 days.

I recently argued, in the Journal of Medical Ethics, that the current limit for embryo research should be extended to 28 days to permit research that will further explore our origins as well as potentially provide new therapeutic possibilities to reduce developmental abnormalities and miscarriage.

This conversation is something the Progress Educational Trust (PET), the charity which publishes BioNews, has been advocating for many years. Recent work they have accomplished includes a proposal to the 'My Science Inquiry' launched by the House of Commons Science and Technology Committee. Sandy Starr, deputy director of PET gave oral evidence to the committee advocating for this conversation to be had by government, as it is already an ongoing debate within the scientific community. PET also held their annual conference in 2016, which focused on the 14-day limit on human embryo research, and that featured Baroness Mary Warnock, who was chair of the committee that originally proposed the limit in 1984.

There are a number of reasons why research on embryos between 14 and 28 days, often referred to as the 'black box' period of development, is now ready to be initiated. Several of these are emphasised in my paper.

Firstly, the 'black box' period is when the basic body plan and the formation of critical cell types, tissues, and some organs is initiated. These include germ cells, which are not only essential for the next generation, but are also the early progenitors of the nervous system, blood cells and the heart, and the placenta. It is known that even a subtle defect can have a devastating effect on subsequent development. While we know something about how these develop in model organisms such as the mouse, there are clear differences with human embryos, making it difficult to infer results between species. We also can't yet rely on new stem cell-based models of early human embryos without first carrying out detailed comparisons with the real thing.

It could be argued that 28 days is not long enough. Whilst this is certainly a thought-provoking point, we are already able to obtain embryonic tissues from 28 days and beyond and older fetal tissue to use in scientific research eg, from an aborted fetus. It is also important to consider the need for a 'limit'. If there is not one at all, there is no compromise, discontent, and it could complicate the regulatory system.

In conversations surrounding the 14-day limit there are differing ethical opinions. I argue that in order for those trying for a baby to have legitimate reproductive autonomy, they should have the appropriate assistance and opportunity to produce, at the very least, a healthy child. I also focus on the need to differentiate between 'research' embryos and 'reproductive implanted embryos' ie, the research embryos in question are those whose location will remain in a petri dish.

It is absolutely crucial to outline the importance of a robust regulatory body. In the UK, we are lucky to have the Human Fertilisation and Embryology Authority (HFEA), which means there is government oversight making sure fertility clinics and research centres comply with the law, this extends to human embryo research. For example, in 2016, Dr Kathy Niakan was not just the first person in the UK to be granted a license from the HFEA to use genome editing techniques on human embryos, but the first anywhere to have this type of research sanctioned by a regulatory body. (See BioNews 835).

With any significant legislative change that will directly impact the population, significant public debate must be instigated. Public opinion must be widely surveyed and considered, because any decisions like this should not just be one made by a select few individuals. This can be seen with another significant change in the HFE Act, the addition of mitochondrial donation regulations in 2015, which is an example where public engagement was very important. It gave the Government license to make the changes in the HFE Acts, knowing that there was broad support for the use of the methods to avoid mitochondrial disease.

As I conclude in the paper, just because something has once worked does not mean it should stay the same or not strive to be improved. The 14-day limit has become limiting and the conversation around extension must continue.

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The 14-day limit should be extended to 28 days - BioNews

Embryology

New Agriculture Scholarship Offered in Honor of the Late Harold Tutvedt – Flathead Beacon

News & FeaturesSeniors at Flathead and Glacier high schools can apply for funding to attend Montana State University College of Agriculture

By Myers Reece // Feb 16, 2021

Seniors at Glacier and Flathead high schools can now apply for a new agricultural college education scholarship named after the late Harold Tutvedt, a well-known West Valley farmer who passed away in 2018.

The $2,000 scholarship will be awarded to a senior who intends to pursue a degree at Montana State Universitys College of Agriculture and Natural Resources, offering students yet another opportunity in a school district already reputed for its robust agricultural curriculum through the H.E. Robinson Agricultural Education Center.

The application deadline for the Harold Tutvedt Memorial Scholarship is March 10. Seniors at either Kalispell high school can apply by contacting their respective college and career center.

Its huge, Brian Bay, a teacher at the Agricultural Education Center in Kalispell, said. A scholarship of this size directly for a student going to Montana State University is significant. It will make a huge difference for whoever gets it.

The MSU College of Ag is known nationally, he added, and theres the history of the Tutvedts and the role they have played in our community and agriculture. Its really neat.

The ag center welcomes between 300 and 350 students each year, including 21 seniors this year who will be the target audience of the new scholarship, although a number of them have already committed to plans and schools other than MSU, Bay said.

The center opened its doors in 1978, but Flathead High School has had an agricultural program since 1917, while Future Farmers of America has been established in town since 1930 and high school students have farmed the land on which the ag center sits since the 1940s, including generations of Tutvedts who attended Kalispell public schools.

Harold would have farmed this ground when he was a student, Bay said.

Harold Tutvedt, the second child of Norwegian immigrants, was born in a leased farmhouse with no power or running water off Clark Drive in West Valley in 1929 and spent his entire life in agriculture, moving from farming with horses to driving the big green auto steer combines that he loved so much, according to his 2018 obituary. He attended Flathead High School and Montana State University.

Mike Kelly, director of the Flathead High career center, said the Tutvedt family came up with the idea of an agricultural education scholarship following Harolds death. Kelly, who helps kids devise their post-high school steps, notes that agricultural education has grown significantly over the years into areas including embryology, soil science, innovative concepts in animal husbandry and raising plants, and more.

The field has broadened quite a bit to include many things other than the stereotype of what many think of farming, planting crops, raising cattle, dairy farming, riding a tractor, he said. Theres certainly all those components, but there are a lot of other things that go along with it.

The scholarship comes as the ag centers hundreds of high school students are newly enjoying updated facilities, funded by the passage of a school bond package in 2016. Bay called the renovations terrific.

Were so pleased with this place, he said.

People interested in contributing to the scholarship fund can make donations to the Harold Tutvedt Memorial Scholarship C/O Blue Mountain Community Foundation, P.O. Box 603, Walla Walla, WA 99362.

For questions about the application process, contact Mike Kelly at (406) 751-3661 or kellymi@sd5.k12.mt.us.

If you enjoy stories like this one, please consider joining the Flathead Beacon Editors Club. For as little as $5 per month, Editors Club members support independent local journalism and earn a pipeline to Beacon journalists. Members also gain access to http://www.beaconeditorsclub.com, where they will find exclusive content like deep dives into our biggest stories and a behind-the-scenes look at our newsroom.Join Now

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New Agriculture Scholarship Offered in Honor of the Late Harold Tutvedt - Flathead Beacon

Embryology

‘I split with my ex then chaos set in’: Why we need to talk about the flux years – Metro.co.uk

Nell Frizzells new book explores the chaotic years between adolescence and midlife (Picture: Bekky Lonsdale/Getty)

At 28, my life went into a totally catastrophic period of personal and professional chaos, of change and transformation, says Nell Frizzell, now 36.

I threw away the security of a relationship, confronted the finite nature of my fertility, acted at times with careless depravity and took on, eventually, a whole new identity.

The future shed pictured with her ex, with whom shed split after six years, was replaced with the myriad possibilities of single life but it also emphasised the metaphorical ticking clock.

If she did want a baby, then when, how, why and with whom?

Adolescence and menopause encapsulate monumental periods in life but theres no term to describe what happens in between. Its why writer Nell set herself the bold task of creating a linguistic shorthand for these nameless but equally fundamental years. She settled on the flux.

I like that it captures the psychological chaos, physical bodily elimination and emotional fluctuation that happens between adolescence and midlife, says Nell, who explores the flux in her new book, The Panic Years: Dates, Doubts And The Mother Of All Decisions.

She highlights that the choices we make from our twenties to our early forties are often heavily influenced by one question: whether we should have a baby. This impacts on all aspects of our life, including dating, which job to do and where to live.

Nells own flux was triggered by the end of that six-year relationship. Already an unduly catastrophic thinker, the sense of panic was amplified by the fact her mum went through the menopause at 40.

Every month Id get my period and think, Thats another potential future gone, and I didnt know how many of those eggs I had left, but Im glad it pushed me to make a decision, says Nell, who now lives in Oxford with partner Nick and their three-year-old son.

Motherhood didnt herald an epiphany for Nell but it did prompt her to ponder the extent to which we endlessly ruminate about becoming a parent.

Sometimes the further away you get from something, the easier it is to see the towering thing above you, and the further I got away from 28, the easier it was to see the looming presence motherhood has always had in my life, she says.

Not only what it meant and the compromises Id need to make but the way the men in my life had been conditioned to think about fertility, the way we talk about female desire and maternal love. All those things deeply altered my life in a way I wasnt prepared for.

Throughout the book Nell gamely shares brutally honest anecdotes from her own flux, including the hopeful but doomed flings, the anguish of birthdays, weddings and baby showers, as well as her own messy journey to becoming a mum. But she also examines the wider societal issues.

I still find contraception a deeply troubling and sexist phenomenon, she says. The average cost of childcare in this country is unsustainable and the rate of successful interventions in terms of egg freezing and IVF are much lower than I thought.

On those two points, the numbers speak for themselves: it costs 6,800 per year for a part-time nursery place, says The Money Advice Service, and around four in five cases are unsuccessful, according to the Human Fertilisation and Embryology Authority.

All these things can look like separate quandaries but they all feed into the same giant flux so of course we have a hard time trying to navigate them simultaneously, says Nell. And Im a white, educated woman operating from a huge sense of privilege. What must it be like to be a person of colour or low income, a single parent, or from the LGBTQ community?

While Nells flux ultimately led to a baby, the book isnt about that one narrative.

I hope child-free people, by choice or otherwise, can find things in it that really speak to them because whats surprised me is that the people Id least expect, who are leading very different lives to me, told me they can identify with the things Im describing, she says.

Nells only just started having frank discussions with her friends about this topic.

Im the queen of oversharing, someone who never shies away from the more revolting sides of having a human body, but I shied away, and still do, from saying to people, Do you want to have a baby? Its such a loaded question, she says.

Only certain people have the right to ask that question and in certain circumstances but I do think its a conversation people should feel more able to have. It feels like we all skirt around something thats quite fundamental to the way we live our life.

To hold our feelings up to the scrutiny of the world can be scary but its healthy to say what you want.

Nell Frizzells The Panic Years is out now

Do you have a story to share?

Get in touch by emailing MetroLifestyleTeam@Metro.co.uk.

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'I split with my ex then chaos set in': Why we need to talk about the flux years - Metro.co.uk

Cell Biology

Avance Biosciences Expanding Houston Campus in Support of Cell and Gene Therapy Drug Development – BioSpace

HOUSTON, Feb. 16, 2021 /PRNewswire/ -- Avance Biosciences Inc., a leading CRO providing GLP/GMP-compliant assay development, assay validation, and sample testing services supporting biological drug development and manufacturing, announced today that its Houston facility, which successfully passed an inspection by the U.S. Food and Drug Administration in Oct 2018, is undergoing major expansion to handle rapidly growing demand for their services.

The new facility, expected to be completed by Q3 2021, is located adjacent to the current facility and will expand the Houston campus by an additional 5,500 square feet. The new facility will be devoted to cell-based assay services and enable Avance to better address the specific needs of their GMP clients. Additionally, Avance is expanding their mammalian cell culture related assay capabilities including: mycoplasma testing, adventitious agents testing, sterility, potency, and others.

As a provider of genomics and biological testing services, Avance Biosciences offers a broad range of molecular biology and microbiology assays in compliance with current Good Manufacturing Practices (21 CFR Parts 210 & 211) and Good Laboratory Practices (21 CFR Part 58) to support its clients' regulatory submissions.

Avance's CEO, Dr. Xuening Huang commented, "We take a partnership approach with our clients and that means an extended relationship; from discovery to development to clinical testing and on to manufacturing. Our most recent expansions will ensure that we can keep pace with our customer's increased needs when ramping up development and manufacturing activities. Our primary goals are to deliver world-class service and complete customer satisfaction."

Avance's Vice President of Sales and Marketing, Cal Froberg commented, "It's clear there is tremendous growth in the development of cell and gene therapies and we're proactively managing resources to handle increased market demand for related support services. The industry is expanding rapidly and Avance is positioned well to address the specific needs of these customers."

This most recent expansion comes on the heels of another 7,500 square foot expansion completed in 2020 which has significantly increased Avance's NGS and ddPCR capabilities. This facility has been pivotal in addressing gene therapy development support needs such as: edited gene testing, gene integration assays, and DNA/RNA biodistribution studies.

Recently, Avance Biosciences was recognized as a top 10 Genomics Solutions Company for 2020. Current and future expansion plans will serve to solidify this position among the premier providers in this space.

About Avance Biosciences

Avance offers cGMP/GLP compliant genomics biological testing services in support of drug development and manufacturing. Its leading scientists have designed, validated, and tested thousands of assays under cGMP/GLP regulations for the FDA, EPA, and European and Japanese regulatory agencies. Avance's team has extensive knowledge and experience working with scientists, QA/QC professionals and project managers from over 100 pharmaceutical and biotechnology companies and organizations throughout the world.

Contact

Xuening Huangxuening.huang@avancebio.com877-909-52109770 West Little York RoadHouston, TX 77040 USA

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Avance Biosciences Expanding Houston Campus in Support of Cell and Gene Therapy Drug Development - BioSpace

Cell Biology

Beating the resistance: WVU scientists target antibiotic-resistant infections with $1.4M DOD grant – My Buckhannon

MORGANTOWN Antibiotic resistance is not exclusively a health issue.

Its a national security threat, as the Department of Defense has tapped a team ofWest Virginia Universityscientists to help exterminate the enemy infectious biological agents.

With the aid of $1.4 million-grant from the DODs Defense Threat Reduction Agency, researchers, led byMariette Barbierof theWVU School of Medicine, will aim to develop small molecule and antibody therapeutics to treat infections prone to antibiotic resistance.

Nearly three million people in the United States get an antibiotic-resistant infection each year. Of those, more than 35,000 die, according to the Centers for Disease Control and Prevention. This happens when bacteria and fungi thrive because theyre too powerful for the drugs designed to kill them. By 2050,experts have predicted that more people might diefrom these antibiotic-resistant infections than by cancer that is unless research like Barbiers is successful.

Barbier said her project is twofold: 1) It prepares the DOD for bioterrorism risks. 2) It presents potential solutions to the ever-growing public health challenge of antibiotic resistance.

One of the missions of the DOD is preparedness against biological threats, said Barbier, assistant professor in theDepartment of Microbiology, Immunology and Cell Biology. Some bacteria are potential bioterror agents, but there are also bacteria within those same families that are responsible for causing hospital-acquired infections. By focusing on these species of bacteria, were casting a broad net to address potential biological threats as well as infections that afflict everyday patients.

Barbiers team will employ a search and destroy approach by combining antibodies with antimicrobials. Antibodies are blood proteins that seek out and bind to specific antigens on pathogens. Combining them with antimicrobial molecules can create a therapeutic potent enough that, Barbier believes, can effectively treat those stubborn infections.

Joining her areSlawomir Lukomski, associate professor, andAlexander Horspool, postdoctoral fellow and the scientist in charge of antibody discoveries within theWVU Vaccine Development Center. In addition, the team will collaborate with researchers from the Massachusetts Institute of Technology and University of Maryland on this project.

One specific species targeted by the team includesBurkholderia, a rod-shaped bacterium considered a potential biological warfare agent that could target livestock and humans. The team will also target the bacteriumPseudomonas aeruginosa, which causes a form of pneumonia known to affect cystic fibrosis patients. Many types of bacteria, such as these, do not have preventative measures such as vaccines.

The types of infections caused by these organisms are really broad, Barbier said. Youve got respiratory infections, skin infections, bladder infections, and youve got all sorts of infections resulting from surgical procedures.

One reason antibiotics have a hard time conquering bacteria is due to their evolving versatility. Bacteria can adapt to new and changing environments. If onePseudomonas aeruginosacell, for example, survives a flurry of antibiotics, it can multiply into even more cells that are impervious to traditional treatment.

With this project, were hoping to develop new ways to fight these infections or even prevent them to start with, Barbier said. What weve realized is how powerful our own immune systems and antibodies can be. So what we propose here is to harness that aspect of our immune system and use it for treatment.

An added element to the project will be the utilization of artificial intelligence and machine learning techniques that will be developed at the MIT Computer Science and Artificial Intelligence Lab. Lukomski, who has identified novel antigens againstBurkholderia, will screen molecules with potential antimicrobial properties in his lab before taking the data to feed into a computer system.

Using artificial intelligence and machine learning will allow us to make reiterative calculations in order to predict whether compounds could have potential therapeutic effects, he said.

Rather than spending days and possibly months in a lab screening compounds which are expensive to make and difficult to obtain scientists can screen billions of molecules in a few hours using a super computer, Barbier added.

Were not just addressing current problems, she said. Were also looking at the future in terms of making predictions as to what treatment could be efficacious to help us fight the next bacterial pandemic.

The project stems from June 2019, when Barbier joined members of the WVU VDC at the BIO International Convention the worlds largest global biotech partnering event. At this conference, Barbier and the VDC met with representatives from DTRA. In November 2019, representatives from DTRA visited WVU to meet with members of the WVU Health Sciences Center and Corporate Relations Team, where the idea for this project came to life.

As a result of the visit, Barbier was able to connect with collaborators from the University of Maryland and MIT. The three universities will work together to accomplish the goals of this grant.

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Beating the resistance: WVU scientists target antibiotic-resistant infections with $1.4M DOD grant - My Buckhannon

Cell Biology

What rules govern structure of membraneless organelles? – UB Now: News and views for UB faculty and staff – University at Buffalo Reporter

In cells, numerous important biochemical functions take place within spherical chambers made from proteins and RNA.

These compartments are akin to specialized rooms inside a house, but their architecture is radically different: They dont have walls. Instead, they take the form of liquid droplets that dont have a membrane, forming spontaneously, similar to oil droplets in water. Sometimes, the droplets are found alone. Other times, one droplet can be found nested inside of another. And these varying assemblies can regulate the functions the droplets perform.

A study published on Feb. 8 in Nature Communications explores how these compartments, also known as membraneless organelles (MLOs) or biomolecular condensates, form and organize themselves. The research lays out physical rules controlling the arrangement of various types of synthetic MLOs created using just three kinds of building materials: RNA and two different proteins, a prion-like polypeptide (PLP) and an arginine-rich polypeptide (RRP).

The project brought together a team from UB and Iowa State University.

Different condensates can coexist inside the cells, says first author Taranpreet Kaur, a PhD student in physics in the UB College of Arts and Sciences. They can be detached, attached to another condensate, or completely embedded within one another. So how is the cell controlling this? We found two different mechanisms that allowed us to control the architecture of synthetic membraneless organelles formed inside a test tube. First, the amount of RNA in the mixture helps to regulate the morphology of the organelles. The other factor is the amino acid sequence of the proteins involved.

These two factors impact how sticky the surfaces of the condensates are, changing how they interact with other droplets, says Priya Banerjee, UB assistant professor of physics, and one of two senior authors of the paper. In all, we have shown using a simple system of three components that we can create different kinds of organelles and control their arrangement in a predictive manner. We suspect that such mechanisms may be employed by cells to arrange different MLOs for optimizing their functional output.

Davit Potoyan, assistant professor of chemistry at Iowa State, is the studys other senior author.

The experiments were done on model systems made from RNA and proteins floating in a buffer solution. But the next step in the research already underway is to conduct similar studies inside a living cell.

Going back to our motivations in researching MLOs, the big questions that started the field were questions in cell biology: How do cells organize their internal space? Banerjee says. The principles we uncover here contribute to the knowledge base that will improve understanding in this area.

Research on MLOs could lead to advancements in fields such as synthetic cell research or new materials for drug delivery.

We are in the process of learning the biomolecular grammar that may be a universal language used by cells for taming their inner cellular complexity. We hope one day to utilize this knowledge to engineer artificial protocells with custom-designed functionalities inspired by nature, Potoyan says.

In addition to Banerjee, Potoyan and Kaur, co-authors of the study included Iowa State chemistry postdoctoral researcher Muralikrishna Raju; UB physics PhD student Ibraheem Alshareedah; and UB physics postdoctoral researcher Richoo Davis.

The study was supported by the National Institute of General Medical Sciences, part of the U.S. National Institutes of Health, and the U.S. National Science Foundation (NSF). The team also received assistance from two NSF-funded resources: the UB North Campus Confocal Imaging Facility and the Extreme Science and Engineering Discovery Environment.

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What rules govern structure of membraneless organelles? - UB Now: News and views for UB faculty and staff - University at Buffalo Reporter

Cell Biology

Hoxton Farms Bags US$3.75M To Bring Back Fat By Cultivating It From Animal Cells – Green Queen Media

London-based biotech startup Hoxton Farms has raised 2.7 million (approx. US$3.75 million) in a seed funding round for its cultivated fat technology. Using cell biology and mathematical modelling, the company grows a slaughter-free and sustainable better kind of fat directly from animal cells in bioreactors. Hoxton Farms says their cultivated fat ingredients will help elevate the sensory and functional properties of alternative proteins.

Hoxton Farms has announced a 2.7 million (approx. US$3.75 million) seed funding round led by San Francisco-based venture capital firm Founders Fund created by Peter Thiel, with participation from Backed, Presight Capital, CPT Capital and the dedicated alternative protein rolling fund on AngelList, Sustainable Food Ventures (SFV). Several angel investors also joined the seed round.

The London-headquartered biotech says that the capital will go towards expanding its interdisciplinary science team in their new lab in Hoxton, where it will continue developing its cultivated animal fat production platform.

Our mathematical approach drives everything we do at Hoxton Farms. We simulate the entire process computationally, from biopsy to bacon.

It plans to use its proprietary computational models to reduce the cost of manufacturing its purified animal fat in bioreactors, with the aim of building customer partnerships to supply its product to the alternative protein industry, starting with plant-based meat firms who are looking for better-tasting alternatives to plant oils.

Our mathematical approach drives everything we do at Hoxton Farms. We simulate the entire process computationally, from biopsy to bacon. This digital twin allows us to optimise every raw input in parallel, massively improving the cost-efficiency and performance of our cultivated fat for our customers, explained Ed Steele, co-founder of Hoxton Farms.

Hoxton Farms technology is aimed squarely at solving the challenge of finding low-cost, effective yet sustainable alternatives to traditional animal fat often described as the crucial ingredient in meat that gives the sensory experience that consumers crave. Cultivated animal fat, which is grown directly from the cells of animals, would also offer the functional textural, cooking qualities and appearance that alternative proteins producers have struggled to replicate using plant-based oils and fats.

Cultivated fat is the hero ingredient for meat alternatives, and it will solve a huge problem in this growing industry. We believe the future of meat alternatives will be a blend of plant-based protein and cultivated fat.

We want to bring back fat: its the single most important ingredient in the meat that we eat. The technology were developing will allow us to customise fat for any application and were making it healthier too, said Dr. Max Jamilly, co-founder of Hoxton Farms.

Cultivated fat is the hero ingredient for meat alternatives, and it will solve a huge problem in this growing industry. We believe the future of meat alternatives will be a blend of plant-based protein and cultivated fat.

Commenting on the decision to back Hoxton Farms, Eric Scott, principal at leading investor Founders Fund, said: The market for plant-based meat has exploded in recent years, especially during the pandemic. But plant-based meat has a long way to go and thats because its missing out on real cell-based animal fat.

The teams ability to tailor the precise sensory and functional properties of fat allows them to produce exactly what their customers need. Hoxton Farms has the potential to change an industry, Scott continued.

Plant-based meat has a long way to go and thats because its missing out on real cell-based animal fat.

While the number of startups educated to offering solutions to animal fats remains small, Hoxton Farms is by no means alone. Belgian B2B startup Peace of Meat, for instance, produces cultivated fat and texturing ingredients and has recently been bought out by Israeli cultured meat firm Meat-Tech 3D as part of its commercialisation strategy to launch hybrid alternative meats made from both plant and cell-based ingredients on the market.

Another food tech, Cubiq Foods, based in Barcelona, is creating cell-based fats that are high in omega-3 fatty acids. According to some reports, Cubiq Foods are already in talks with cultivated companies such as Mosa Meat for a potential collaboration.

Motif FoodWorks, on the other hand, are aiming to create a plant-based fat that has the attributes of animal-derived fats, which will help elevate the taste, texture and appearance of vegan meat and dairy alternatives.

Lead image courtesy of Hoxton Farms.

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Hoxton Farms Bags US$3.75M To Bring Back Fat By Cultivating It From Animal Cells - Green Queen Media

Cell Biology

Cytovia Therapeutics and Cellectis Partner to Develop TALEN Gene-Edited iPSC-Derived Natural Killer Cells – BioSpace

CAMBRIDGE, Mass. and NEW YORK, Feb. 16, 2021 (GLOBE NEWSWIRE) -- Cytovia Therapeutics, Inc., a biopharmaceutical company developing allogeneic off-the-shelf gene-edited Natural Killer (NK) and Chimeric Antigen Receptor (CAR)-NK cells derived from induced pluripotent stem cells (iPSCs), and Cellectis (Euronext Growth: ALCLS - Nasdaq: CLLS) a clinical-stage biopharmaceutical company focused on developing immunotherapies based on gene-edited allogeneic CAR T-cells (UCART), announced today that they have entered into a strategic research and development collaboration to develop TALEN gene-edited iPSC NK and CAR-NK cells.

The financial terms of the partnership include up to $760 million of development, regulatory, and sales milestones from Cytovia to Cellectis for the first 5 TALEN gene-edited iPSC-derived NK products (partnership products). Cellectis will also receive single-digit royalty payments on the net sales of all partnered products commercialized by Cytovia. Cellectis will receive an equity stake of $15 million in Cytovia stock or an upfront cash payment of $15 million if certain conditions are not met by December 31, 2021, as well as an option to invest in future financing rounds.

We are excited to collaborate with Cellectis, a gene-editing pioneer and leader in the development of gene-edited allogeneic cancer therapies, to further accelerate Cytovias NK cell programs, said Dr. Daniel Teper, Chairman & CEO of Cytovia Therapeutics. Cellectis has a deep understanding and proven expertise in gene-edited cell therapies, and their gene editing technology, TALEN, will yield NK and CAR-NK treatments with improved potency, persistence, and safety for a variety of cancers, including solid tumors. We look forward to leveraging Cellectis insights and experience to help move Cytovias CAR-NKs into clinical trials by 2022.

Cellectis will develop custom TALEN, which Cytovia will use to edit iPSCs. Cytovia will be responsible for the differentiation and expansion of the gene-edited iPSC master cell bank into NK cells and will conduct the pre-clinical evaluation, clinical development, and commercialization of the mutually-agreed-upon selected therapeutic candidates. Cellectis is granting Cytovia a worldwide license to its TALEN gene-editing technology, enabling Cytovia to modify NK cells addressing multiple gene targets for therapeutic use in several cancer indications.

We are thrilled to partner with Cytovia, a pioneer in the development of NK cells derived from iPSCs, said Dr. Andr Choulika, CEO of Cellectis. We are looking forward to this collaboration and the opportunity to further expand the potency of our proprietary TALEN gene-editing technology to iPSCs and CAR-NKs. Down the road, this collaboration should allow for NK cell therapies to be made available to cancer patients, which is very much in line with Cellectis mission to provide life-saving product candidates to address unmet patient needs in this field.

About CellectisCellectis is developing the first of its kind allogeneic approach for CAR-T immunotherapies in oncology, pioneering the concept of off-the-shelf and ready-to-use gene-edited CAR T-cells to treat cancer patients. As a clinical-stage biopharmaceutical company with over 20 years of expertise in gene editing, Cellectis is developing life-changing product candidates utilizing TALEN, its gene editing technology, and PulseAgile, its pioneering electroporation system to harness the power of the immune system in order to target and eradicate cancer cells.

As part of its commitment to a cure, Cellectis remains dedicated to its goal of providing lifesaving UCART product candidates to address unmet needs for multiple cancers including acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (B-ALL) and multiple myeloma (MM).

Cellectis headquarters are in Paris, France, with additional locations in New York, New York and Raleigh, North Carolina. Cellectis is listed on the Nasdaq Global Market (ticker: CLLS) and on Euronext Growth (ticker: ALCLS). For more information, visit http://www.cellectis.com.

Follow Cellectis on social media: @cellectis, LinkedIn and YouTube.

TALEN is a registered trademark owned by Cellectis.

About Cytovia TherapeuticsCytovia Therapeutics Inc. is a biotechnology company that aims to accelerate patient access to transformational immunotherapies, addressing several of the most challenging unmet medical needs in cancer. Cytovia focuses on Natural Killer (NK) cell biology and is leveraging multiple advanced patented technologies, including an induced pluripotent stem cell (iPSC) platform for CAR (Chimeric Antigen Receptors) NK cell therapy, next-generation precision gene-editing to enhance targeting of NK cells, and NK engager multi-functional antibodies. Our initial product portfolio focuses on both hematological malignancies such as multiple myeloma and solid tumors including hepatocellular carcinoma and glioblastoma. The company is establishing R&D and GMP manufacturing operations in the greater Boston area and partners with the University of California San Francisco (UCSF), the New York Stem Cell Foundation (NYSCF), the Hebrew University of Jerusalem, INSERM, and CytoImmune Therapeutics.Learn more at http://www.cytoviatx.com and follow Cytovia Therapeutics on Social Media (Facebook, LinkedIn, Twitter, and Youtube).

About Gene-Edited, iPSC-derived NK CellsChimeric Antigen Receptors (CAR) are fusion proteins that combine an extracellular antigen recognition domain with an intracellular co-stimulatory signaling domain. Natural Killer (NK) cells are modified genetically to allow insertion of a CAR. CAR-NK cell therapy has demonstrated initial clinical relevance without the limitations of CAR-T, such as Cytokine Release Syndrome, neurotoxicity or Graft vs Host Disease (GVHD). In addition, CAR-NKs are naturally allogeneic, available off-the-shelf and may be able to be administered on an outpatient basis. Recent innovative developments with the induced pluripotent stem cell (iPSC)-derived CAR-NKs, an innovative technology, allow large quantities of true off-the-shelf, homogeneous genetically modified CAR NK cells to be produced from a gene-edited iPSC master cell bank, and thus hold promise to expand access to cell therapy for many patients.

For further information, please contact:

Cellectis Media contacts:Margaret Gandolfo, Communications Manager, 646-628-0300, margaret.gandolfo@cellectis.comConor McGoldrick, Zeno Group, Assistant Account Executive, 914-355-0927, Conor.Mcgoldrick@zenogroup.com

Cellectis IR contact:Simon Harnest, SVP, Corporate Strategy and Finance, 646-385-9008, simon.harnest@cellectis.com

Cytovia Investor Relations contact: Anna Baran-DjokovicVP of Investor Relations646-355-1787anna@cytoviatx.com

Cytovia Media contact: Chris MaggosLifeSci Advisors+41 79 367 6254chris@lifesciadvisors.com

Disclaimer

This press release contains forward-looking statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by words such as at this time, believe, expected, forward looking, promising and will, or the negative of these and similar expressions. These forward-looking statements, are based on our managements current expectations and assumptions and on information currently available to management. These forward-looking statements are made in light of information currently available to us and are subject to numerous risks and uncertainties, including with respect to the duration and severity of the COVID-19 pandemic and governmental and regulatory measures implemented in response to the evolving situation. Furthermore, many other important factors, including those described in our Annual Report on Form 20-F and the financial report (including the management report) for the year ended December 31, 2019 and subsequent filings Cellectis makes with the Securities Exchange Commission from time to time, as well as other known and unknown risks and uncertainties may adversely affect such forward-looking statements and cause our actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.

PDF available at: http://ml.globenewswire.com/Resource/Download/c6bbee7d-f56e-400c-a6a4-28586a9e4851

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Cytovia Therapeutics and Cellectis Partner to Develop TALEN Gene-Edited iPSC-Derived Natural Killer Cells - BioSpace

Cell Biology

Research Associate in Stem Cells and Regenerative Medicine job with KINGS COLLEGE LONDON | 246711 – Times Higher Education (THE)

Job descriptionThe Centre for Stem Cells & Regenerative Medicine is located in Guys Hospital.It is internationally recognized for research on adult and pluripotent stem cells and is a focus for cutting-edge stem cell research currently taking place across the College and its partner NHS trusts, as part of Kings Health Partners. Through the Centre, Kings aims to drive collaboration between scientists and clinicians to translate the potential of stem cells into clinical reality for patients.Applications are invited for a postdoctoral researcher funded as part of the PIs Wellcome Clinical Fellowship, and will work with a dynamic group of scientists focussed on reproductive biology, early embryonic development and the causes of infertility. The post holder will contribute to the regenerative medicine theme and will be involved in the generation and processing of single cell experiments using a variety of techniques.This is an exciting opportunity following our recent work (Sangrithi et al. 2017, Dev Cell & Lau et al. 2020, Dev Cell). The project aims to discover the function of genes on the X-chromosome in male germline stem cells (spermatogonia) and their role in idiopathic and sex chromosome aneuploidy associated infertility. We aim to understand physiological gene regulatory networks functional in spermatogonial stem cells using a combination of single-cell methods, to explain how perturbation in X-gene dosage in SSCs may cause infertility. The postholder will also identify and validate candidate disease bio-markers.This post will be offered on an a fixed-term contract until 05/04/2026This is a full-time post - 100% full time equivalent

Key responsibilities Carry out world class research. Are adept at working in a wet lab setting with experience in designing and executing experiments. Familiarity in single cell work nucleic acid manipulation is desirable Communicate results effectively in writing and orally Contribute to publications arising from the research projects Keep clear and up-to-date records of work Attend and present at seminars, journal clubs and conferences Contribute to collaborative atmosphere of the department Share skills by training others Comply with all relevant safety legislation to ensure a safe working environment Take part in public engagement activities To support grant writing, for maintaining the continual research in this domain, e.g. Fellowships Post holder will be expected to plan and prioritise their own workload, with competing and shifting priorities under pressure of deadlinesThe above list of responsibilities may not be exhaustive, and the post holder will be required to undertake such tasks and responsibilities as may reasonably be expected within the scope and grading of the post.

Skills, knowledge, and experience

Essential criteria PhD awarded in the biological sciences Excellent general knowledge of molecular biology Knowledge of cell biology Knowledge of flow cytometry Relevant postdoctoral experience Experience in a molecular biology research lab Excellent record keeping / attention to detail Organized and systematic approach to research Pro-active, enthusiastic, positive attitude Self-motivated, with the ability to work under pressure & to meet deadlines Keen interest in infertility and regenerative medicine Ability to think strategically

Desirable criteria Understanding of the biology of germ cells and embryo development Previous experience in working with the laboratory mouse ES cell culture experience General knowledge of computational tools for single cell RNAseq Ability to make collaborative and independent decisions*Please note that this is a PhD level role but candidates who have submitted their thesis and are awaiting award of their PhDs will be considered. In these circumstances the appointment will be made at Grade 5, spine point 30 with the title of Research Assistant. Upon confirmation of the award of the PhD, the job title will become Research Associate and the salary will increase to Grade 6.Further informationABOUT THE SCHOOLThe School of Basic & Medical Biosciences is led by Professor Mathias Gautel and comprises five departments with a wide range of expertise and interests. Using a bench to bedside approach, the School aims to answer fundamental questions about biology in health and disease and apply this to the development of new and innovative clinical practise, alongside providing a rigorous academic programme for students.DepartmentsThe Centre for Human & Applied Physiological Sciences (CHAPS) uses an integrative and translational research approach focusing on fundamental questions about human physiological function in health and disease to explore 3 research themes: skeletal muscle & aging, sensory-motor control & pain and aerospace & extreme environment adaptation.The Centre for Stem Cells & Regenerative Medicine focuses on cutting-edge stem cell research, how stem cells interact with their local environment and how these interactions are important for developing effective cell therapies in the clinic.The Department of Medical & Molecular Genetics uses cutting-edge technologies and analysis techniques to explore the mechanistic basis of disease, improve diagnostics and understand the epigenetic mechanisms of gene regulation and RNA processing, working from whole population level to complex and rare disease genomesThe Randall Centre of Cell & Molecular Biophysics takes a multi-disciplinary approach at the interface of Biological and Physical Sciences to explore the underlying mechanisms behind common diseases.St Johns Institute of Dermatology seeks to improve the diagnosis and management of severe skin diseases, through a better understanding of the basic pathogenetic mechanisms that cause and sustain these conditions focussing on cutaneous oncology, genetic skin disorders, inflammatory & autoimmune skin disorders, and photomedicine.About the Department of Centre for Stem Cells & Regenerative MedicineThe Centre for Stem Cells & Regenerative Medicine is led by Professor Fiona Watt, whos laboratory comprises approximately 30 research staff and visiting scientists and is internationally recognised for research on adult and pluripotent stem cells. Along with Professor Watts group there are nine other research groups operating at the Centre, bringing the total number of staff to approximately 80 people.Research at the Centre is focused on how stem cells interact with their local environment, or niche. We believe that an understanding of these interactions is important for developing effective cell therapies in the clinic. Located on the Guys Hospital campus, the Centre acts as a focus for cutting-edge stem cell research taking place across the College and its partner NHS Trusts, as part of Kings Health Partners. To facilitate collaborations within Kings and with external partners, we have opened a Stem Cell Hotel where researchers can access specialist equipment and technical support to study stem cell behaviour at single cell resolution. We also host an international seminar series and run the Stem Cells @ Lunch seminar series to share ideas and unpublished data. Our researchers are committed to public engagement and take part in diverse outreach events.Detailed information about the Centre for Stem Cells & Regenerative medicine can be found in the link below:http://www.kcl.ac.uk/lsm/research/divisions/gmm/departments/stemcells/index.aspx

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Research Associate in Stem Cells and Regenerative Medicine job with KINGS COLLEGE LONDON | 246711 - Times Higher Education (THE)