Immunology

Experts Urge Those with Asthma to Take Extra Care as Wildfires Burn in Western U.S. – Newswise

Newswise ARLINGTON HEIGHTS, Ill. (September 15, 2020) As wildfires continue to burn across western U.S. states with smoke spreading across a large portion of the country, those with respiratory illnesses such as asthma need to be alert to the effects of smoke on their breathing.

Allergist J. Allen Meadows, MD, president of the American College of Allergy, Asthma and Immunology, says its important for everyone but especially children and those who suffer from asthma and other respiratory illnesses -- to stay indoors in order to not be exposed to smoke from the fires.

According to Dr. Meadows, Smoke from fires is a dangerous irritant to the eyes and respiratory system. It can make heart conditions and lung diseases like asthma worse. Children are especially vulnerable because their lungs are less developed, and they are closer to the ground, and thus more likely to take in more smoke.

Dr. Meadows points out that if you smell smoke you should do your best to stay inside. If you have asthma, make sure you are keeping it under control with proper use of your medications, and consult your allergist if are having difficulty breathing. He also recommends that, if you are still able to grocery shop,buy groceries you wont need to cook. Frying or grilling especially can make indoor air pollution worse.

If you must go outside, the Centers for Disease Control and Prevention (CDC) says you shouldnot rely on dustmasks or clothmasks for protection. Paper comfort or dust masks commonly found at hardware stores trap large particles like sawdust and arent useful against smoke. In addition, the cloth masks many people are using as a safeguard from COVID-19 will not protect your lungs from smoke. An N95 mask, properly worn, will offer some protection.

For those near areas where wildfires are burning, keep a supply of your asthma medications ready to go with you. For those who need to evacuate from home and go to a shelter, be sure to let officials know about anyone in your family who has asthma.

Once the wildfires and smoke have been controlled, continue to watch for any asthma symptoms. Contact your healthcare provider if you have trouble breathing, shortness of breath, a cough that wont stop, or other symptoms that do not go away. Call 9-1-1 or go right away to an emergency department for medical emergencies.

About ACAAI

The ACAAI is a professional medical organization of more than 6,000 allergists-immunologists and allied health professionals, headquartered in Arlington Heights, Ill. The College fosters a culture of collaboration and congeniality in which its members work together and with others toward the common goals of patient care, education, advocacy, and research. ACAAI allergists are board-certified physicians trained to diagnose allergies and asthma, administer immunotherapy, and provide patients with the best treatment outcomes. For more information and to find relief, visitAllergyandAsthmaRelief.org.Join us onFacebook,PinterestandTwitter.

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Experts Urge Those with Asthma to Take Extra Care as Wildfires Burn in Western U.S. - Newswise

Immunology

Partner Therapeutics (PTx) Announces the Appointment of Ed Rock as Chief Medical Officer – BioSpace

LEXINGTON, Mass., Sept. 15, 2020 /PRNewswire/ --Partner Therapeutics, Inc. (PTx), Inc. (PTx), a commercial biotechnology company, announced today its appointment of Edwin Rock, MD, PhD to serve as the company's Chief Medical Officer. In his role as CMO, Dr. Rock will oversee clinical development activities for PTx, as well as serve on the Company's executive leadership team.

Dr. Rockhas 16years of leadership experience in the biopharmaceutical industry.Most recently, Edwas Clinical Project Leader and Vice President of Clinical Research at MacroGenics where he led the project team tocompletePhase 3 SOPHIA trialenrollment, to analyzethe studyandthen to write and defend the margetuximab BLA. Prior to MacroGenics, Edserved as Executive Director at Astex Pharmaceuticals where he led the team togenerate theASTRAL-1 guadecitabinetrial protocol, initiatesites in 24 countries, and complete enrollment of 815 patients in21 months.

Prior to Astex, Edwas Senior Director at Otsuka Pharmaceutical Development and Commercialization (OPDC) where he led,oversaw, or defended at Advisory Committeediverse first-in-humanthroughPhase 4 trials of Busulfex,Inqovi, Jynarque, Sprycel,and multiple pre-market new chemical entitiesand biologics. Prior to OPDC, Edwas Medical Director at GSK where he led or served as medical monitor for diverse biologic study products in Phase 1, 2, and 3 trials, including Nucala.

Before GSK, Ed served as a Medical Officer inoncology drug review at the US Food and Drug Administrationwhere he completed 3 NDA reviews and had clinical responsibility for up to 80 INDs. Edholds a B.A. in Biology and Economics fromSwarthmore College, as well as PhD (Microbiology and Immunology,Mark Davis lab)and MD degrees from the Stanford University School of Medicine.He completed medical residency training at Brigham and Women's Hospital in Boston, MA, a medical oncology fellowship at the University of Pennsylvania, and a postdoctoral fellowship in vaccine engineering at Stanford.Following medical residency, Ed worked as a biotech buyside analyst at Leerink Swann and Company.

"We are very happy to welcome Ed to our team to lead clinical development activities," said Debasish Roychowdhury, PTx's Chief Technology Officer. "Ed's expertise in immunology, drug development and regulatory experience will be critical in the ongoing development of Leukine, that is showing tremendous potential in immunomodulation and application across a gamut of diseases."

"I am excited to join the PTx team to strengthen and expand the Leukine franchise and to identify additional products that can benefit from the Company's expertise", said Dr. Rock. "Leukine is an exciting drug that may have therapeutic utility in multiple life-threatening diseases, including cancer, COVID-19 and neurodegeneration, among others. I see tremendous potential for Leukine to help patients across diverse indications with high unmet medical need."

ABOUT LEUKINELEUKINE(sargramostim)is a recombinant yeast derived human granulocyte-macrophage growth factor (rhuGM-CSF) that stimulates the differentiation, maturation and mobilization of cells involved in the innate and adaptive immune response.It is an important immune modulator that has been shown to facilitate cellular signaling, epithelial repair, and other critical processes that enhance the immune response and help defend the body against infection and cancer. Partner Therapeutics acquired the rights to Leukine in 2018. Leukine is held by the U.S. Government in the Strategic National Stockpilefor use during public health emergencies. Leukine is available outside of the United States through a Named Patient Program administered by Tanner Pharma Group.

ABOUT PARTNER THERAPEUTICSPTx is an integrated biotechnology company focused on the development and commercialization of late-stage therapeutics that improve health outcomes in the treatment of cancer and other serious diseases. The company believes in delivering products and supporting medical teams with the purpose of achieving superior outcomes for patients and their families. Visit http://www.partnertx.com

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Partner Therapeutics (PTx) Announces the Appointment of Ed Rock as Chief Medical Officer - BioSpace

Cell Biology

Faculty reimagine their research, research-based courses during COVID-19 – The Brown Daily Herald

Laboratories and lab-based courses have gradually regained momentum, filling up University facultys schedules once again and prompting the redesign of their day-to-day operations and class syllabi. As researchers and professors settle into this abnormal normal, they have reimagined their research-based courses and responsibilities as contributors to the scientific community.

Curating CURE Courses

Course-Based Undergraduate Research Experience, also known as CURE courses, often congregate in a laboratory setting where students are granted the opportunity to design, complete and analyze the results of their own experiments without a known outcome, just like they would do in a professional research lab. Even before the University announced the return of the remainder of students to campus as part of the next phase of reopening, CURE course instructors reinvented aspects of their courses in some cases with assistance from former students to prepare for both completely remote and hybrid instruction.

Assistant Professor of Molecular Biology, Cell Biology and Biochemistry Louis Lapierre and postdoctoral associate Joslyn Mills-Bonal from his lab co-taught BIOL 0600: Genetic Screening in Model Organisms for the first time last fall and are teaching a 12-person section of the course this semester.

For the class, students study how eliminating genes from an organism often used in research a worm-like nematode affects their propensity for aging, according to the Courses@Brown site. Testing predictions for these studies requires procedures and machinery only available in the lab.

A version of BIOL 0600 was offered this summer to high school students as part of Summer@Brown, giving Mills-Bonal the chance to learn from the completely virtual experience and make plans in preparation for the undergraduate-level course.

Given the Universitys recent decision to welcome undergraduate students back to campus in late September, students in the course wont be able to start in the lab until October and will have to be more judicious with how they use their time to run experiments this year, as is typical among scientists, he said.

Professor of Cognitive, Linguistic and Psychological Sciences Ruth Colwill, who is teaching the CURE course CLPS 1195: Life Under Water in the Anthropocene, expressed similar sentiments about her course, which urges students to investigate how environmental pollution can stress aquatic environments by having them observe a striped fish called the zebrafish.

Having prepared for the resumption of in-person classes in October, Colwill rearranged the timeline for the course. The first couple weeks of remote learning is focused on reading primary literature about students research topics, including findings from students who took the course in previous semesters, and planning their projects. Students will then devote any remaining time they have later in the lab to perform those experiments.

Colwill had also prepared for a situation in which the lab would be forced to go fully remote. The point of a CURE is were doing something that nobody knows the answer to, and that wont change, she said, adding that no matter the situation, the course will maintain its collaborative nature.

Over the summer, Colwill worked with prior students and an undergraduate researcher to come up with online components for the course, to reimagine it completely, (and create) a lot of materials, she said.

Colwill has personally used faculty resources provided by the Sheridan Center and Digital Learning and Design to accommodate students learning virtually, such as the Anchor Program. Theyve already created all the materials I need; its just a matter of incorporating them into my course, she said.

Despite the challenges with redesigning these courses, faculty acknowledged several advantages to online or hybrid instruction.

Colwill believes the course may be more inclusive now that discussions will be offered online. This semester, students will post presentations online and receive an entire class period to ask and answer questions, which she hopes will give them time to provide a well thought-out response while alleviating pressure. There can be more depth to the interactions that students have, she said.

Faculty Return to Research

Some researchers previously received the opportunity to return to their labs over the summer, with additional personnel gradually making their way back to the lab benches or the field.

Yet, as faculty dedicated much of their summers planning for hybrid or online courses, they also lost out on time in the lab or had to juggle both tasks. Burnout is a very serious problem, Colwill noted, plus the frustration of not being able to do what you really love doing.

For Colwill, it took several months before she could return to her lab to conduct experiments on her zebrafish and on mice to study their behavior. In those first days back, I rarely saw people at Brown. I would hear maybe a door close, or hear some footsteps in a hallway, she said.

The lapse of time made the work very difficult to interpret, she added. Colwill has not initiated long-term experiments with her mice because of concerns that a change in public health guidance could force her to abruptly pause the research.

When Mills-Bonal returned to the lab in June, she noted that it felt eerie during her later shifts, but the solitude also provided a sense of safety, and now that she has adjusted, its kind of business as usual.

Though the need for shifts minimizes time spent in the lab, which in some cases is less than the length of a full experiment, Mills-Bonal added that the lab members all help each other out.

Lapierre has also implemented Slack for his lab so he may assist researchers at all times, even when he cannot be physically present alongside them.

Professor of Orthopaedics Brett Owens, the principal investigator of the Brown Cartilage Lab at Lifespan and the Brown Sports Injury Laboratory, had to shift his focus from in-lab research on cartilage, a special type of cellular tissue located at body joints, to writing grants and publications. His other lab studying the occurrences of sports injuries continued to analyze data remotely, Owens wrote in an email to The Herald.

Lecturer in Ecology and Evolutionary Biology and paleontologist Amy Chew has spent much of her summers, when she is not teaching at Brown, studying bones in an entirely different atmosphere: outdoors, where she unearths mammalian fossils on the other side of the country to study the toll of climate change upwards of 60 years ago on Wyomings wildlife.

Researchers from multiple institutions have banded together each summer since the 1980s to excavate this region. If you let it drop, theres a significant amount of lost institutional knowledge, Chew said. Driven by the gravity of continuing these investigations despite the COVID-19 pandemic, Chew and about eight of her colleagues from other universities set off to the Bighorn Basin, this time bringing their masks along with their tools.

Paleontological fieldwork is actually probably one of the most amenable kinds of work that you can do for social distancing and isolation, Chew said, describing the openness of the barren badlands.

But not everyone was able to return to the field site. Some researchers funded through their universities were not permitted to travel. As a self-funded researcher, Chew was an exception, but she could no longer have any University undergraduate students join her as they had in years past.

Its really sad because I think the student interest is really a fun, dynamic aspect of doing fieldwork, she said. For people who are students who would like to graduate at a certain time frame, its really unfortunate.

Despite chiseling this years summer at the basin down from a full month to only 10 days in July, the researchers succeeded in making some progress, but altogether, everything is just delayed, including grant and funding applications that depend on preliminary data, Chew said.

Chew is not currently offering student research positions with her because of this uncertainty, and her work with fossils cannot be adapted well to a virtual position.

But Chew added that the biggest impact has perhaps been on students at the Warren Alpert Medical School enrolled in anatomy courses. When she picked up the call for her interview, she was taking a respite from the hours she had been spending in the lab over the course of four days, dissecting bodies and preparing them for medical students, which takes days and days just to do one complete dissection for one block of anatomy coursework.

Typically, students do these dissections in the anatomy lab themselves for hours, studying the organs and tissues that all fit together like a three-dimensional puzzle to form the human body. In doing so, future physicians safely familiarize themselves with the internal structure of the body, preparing for days when they will have to care for patients.

With the pandemic, this safety has taken on a new meaning as students can no longer spend such lengthy portions of time in the lab at risk of exposure to the virus. They will now rotate through, observing the work Chew and other Med School faculty have completed. The impacts of these changes remain to be seen.

In the meantime, just as researchers need to troubleshoot when their experiments go awry whether its researching in the lab, conducting fieldwork or reimagining opportunities to involve undergraduates in the scientific process the administration, faculty and students have problem-solved during this unexpected, global turn of events.

The fall is definitely not without challenges, but theres more support in place, and everyones had a little more experience, so Im optimistic that students will get a good educational experience online, Colwill said.

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Faculty reimagine their research, research-based courses during COVID-19 - The Brown Daily Herald

Cell Biology

The limits of synthetic biology through the origins of SARS-CoV-2 – Drug Target Review

Conspiracy theories about COVID-19 have been spreading since the early days of the outbreak. But how do we know whether a biological entity is artificially made or has occurred naturally? Marc Baiget Francesch explores the capabilities of current scientific approaches in terms of virus engineering and how this applies to the present pandemic.

OVER THE LAST few months, numerous theories relating to the origin of the novel coronavirus SARS-CoV-2 have invaded the internet. Sometimes, these theories can give rise to more interesting discussions than what is originally intended by the authors. For example, the theory that the new coronavirus has been purposely made as a biological weapon would mean that SARS-CoV-2 is a synthetic organism, which simultaneously implies that scientists can create synthetic viruses. How much truth is there in that implication? How far can current technologies go in terms of artificial microorganisms design? To answer these questions, we first need to understand the current state of synthetic biology as a field and acknowledge its limitations.

While making a new virus from scratch is not technically impossible, it would require a level of knowledge that is implausible to imagine in any scientific institution at present

Synthetic biology greatly relies on predictive models and computer simulated structures. Computer programmes use the information collected by years of research in molecular biology, which is stored in huge libraries of microorganisms, molecules and domains, to explore their potential when modified or combined in silico that is, on a computer. The idea of these programmes is to form combinations that, presumably, do not exist in nature in order to analyse potential structures for multiple uses. However, despite in silico models providing valuable information and saving time and money on in vitro experimentation, they are far from perfect.

Professor JA Davies, from the University of Edinburgh, published a paper in the open access journal Life that analysed the current flaws of the engineering approach in synthetic biology. While he recognises that this approach, based on the design-build-test dogma, is interesting and that relying on standard pre-existing parts simplifies the overall design of synthetic structures, it lacks biological understanding.1

In biology, every component from a microorganism has a metabolic cost, ie, the more components you add to a cell, the less energy the cell can direct to each part. Therefore, the fewer parts used for a function, the better. In genetic engineering this is a crucial consideration, since adding new genes normally supposes that pre-existing genes are deleted in order for the organism to be viable. In addition, the interactions between two different pre-existing parts might affect its original function. Hence, as Professor Davies argues, using a novel part, designed for a specific function, might prove easier than trying to reproduce the same function with two pre-existing ones. Ultimately, evolution is based on constant changes of previous structures induced by a huge number of factors and not on the combination of unchanging structures. So, while synthetic biology can cover a lot of unexplored possibilities, it is still far from being an almighty tool or competing with natural evolution.

This brings us to the next question: how capable are current scientific approaches in terms of virus engineering? Researchers can recreate an existing virus from scratch, and this is what many research teams have been attempting since the coronavirus started to spread in order to understand the virus better.2 However, creating a new one is another story. It is possible to create new viruses from original ones; though, there are some restrictions. As aforementioned, synthetic biology relies on the use of pre-existing parts, which means we would need to use different parts of existing viruses and assemble them in order to produce a new virus. Dr Robert F Garry, a microbiologist specialising in virology, commented in Business Insider that there is no consensus on what exactly makes a virus pathogenic.3 Therefore, while making a new virus from scratch is not technically impossible, it would require a level of knowledge that is implausible to imagine in any scientific institution at present. Nevertheless, our current knowledge of molecular science allows us to identify potentially man-made structures or microorganisms.4 This is possible because they are based on pre-existent parts; an engineered virus would have identifiable segments of DNA that belong to other viruses whose sequences are stored in libraries. This means that we should be able to identify if a new virus was artificially designed or is a product of natural evolution.

To study the case of the novel coronavirus, we need to have access to its genetic sequence. This has been a major advancement in epidemiology, as for previous pandemics researchers had to wait from months to years in order to study the microorganism responsible for the outbreak, whereas the structure of SARS-CoV-2 was available within weeks. By analysing its genetic structure, scientists have realised that the backbone of the virus is, indeed, a new one.5 However, this does not mean that the virus was not artificially made; we just know that the backbone was not copied from another virus.

What about prompting an existent virus to mutate? It could be that biotechnologists induced mutations to a known virus in order to produce a novel one, like what we see in nature. However, when scientists evaluated the structure of SARS-CoV-2 and compared it to other viral structures, the closest relative they found was SARS-CoV RaTG13, which showed a 96 percent similarity to the novel coronavirus.6 Although 96 percent may seem a lot, considering the size of SARS-CoV-2, which is close to 30,000 nucleotides long, this four percent difference is quite significant around 1,200 nucleotides.7

Studying evolution and natural processes is key for synthetic biology to expand and become an even more powerful tool

Nevertheless, there may still be some resistance to debunking certain theories. One might argue that, while using known parts of similar viruses, targeted mutations could have been applied to give the virus the ability to attach to human cells which is essentially what makes this virus able to infect humans. One of the most curious facts about the coronavirus is that the receptor binding domain the part that makes SARS-CoV-2 able to attach to human cells was simulated in silico once the sequence of the virus was made available. This sequence showed poor efficiency on the simulations, meaning that nature has found a mechanism that we had not been able to predict.3 If we put together all the facts and reflect on the fact that 75 percent of the new emerging diseases are from zoonotic origin, it appears the theories around SARS-CoV-2 being a man-made virus are quite unrealistic, to say the least.8

Something I have found interesting since the search of the origin of the SARS-CoV-2 started, is that we have confirmed that synthetic biology still has a long way to go. We still need to understand a lot about nature to get a bigger picture of how things work and to grasp all the possibilities that molecular biology has to offer. Studying the evolution of viruses not only benefits the epidemiologists, but also the synthetic biologists, who gain insights into how molecular interactions work. This newfound knowledge can be used to improve current models and propose frameworks for the creation of new molecules. Therefore, one can conclude that studying evolution and natural processes is key for synthetic biology to expand and become an even more powerful tool.

Marc Baiget Francesch is an MSc in Pharmaceutical Engineering and currently works as an Assistant Editor for the International Journal of Molecular Sciences. He also writes articles and innovation grants as a freelancer.

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The limits of synthetic biology through the origins of SARS-CoV-2 - Drug Target Review

Cell Biology

In Ancient Giant Viruses Lies the Truth: Medusavirus Key to Deciphering Evolutionary Mystery – SciTechDaily

DNA exchange between ancient giant viruses and ancient biological cells might have been the key to the evolution of nuclei in eukaryotic cells. Credit: Tokyo University of Science

Giant viruses, like the recently discovered medusavirus, may hold the key to deciphering the evolutionary mystery of the eukaryotic nucleus.

An exchange of genetic material that occurred when ancient giant viruses infected ancient eukaryotic cells could have caused the nucleus of the eukaryotic cell-its defining feature-to form. This is what Professor Masaharu Takemura of the Tokyo University of Science, Japan, suggests in his recent review in the journal Frontiers in Microbiology. His novel evolutionary hypothesis opens doors to new discussions on the subject, bringing us one giant step closer to the truth.

Perhaps as far back as the history of research and philosophy goes, people have attempted to unearth how life on earth came to be. In the recent decades, with exponential advancement in the fields of genomics, molecular biology, and virology, several scientists on this quest have taken to looking into the evolutionary twists and turns that have resulted in eukaryotic cells, the type of cell that makes up most life forms today.

The most widely accepted theories that have emerged state that the eukaryotic cell is the evolutionary product of the intracellular evolution of proto-eukaryotic cells, which were the first complex cells, and symbiotic relationships between proto-eukaryotic cells and other unicellular and simpler organisms such as bacteria and archaea. But according to Professor Masaharu Takemura of the Tokyo University of Science, Japan, These hypotheses account for and explain the driving force and evolutionary pressures. But they fail to portray the precise process underlying eukaryotic nucleus evolution.

Prof Takemura cites this as his motivation behind his recent article published in Frontiers in Microbiology, where he looks into the recent theories that, in addition to his own body of research, have built up his current hypothesis on the subject.

In a way, Prof Takemuras hypothesis has its roots in 2001 when, along with PJ Bell, he made the revolutionary proposal that large DNA viruses, like the poxvirus, had something to do with the rise of the eukaryotic cell nucleus. Prof Takemura further explains the reasons for his inquiry into the nucleus of the eukaryotic cell as such: Although the structure, function, and various biological functions of the cell nucleus have been intensively investigated, the evolutionary origin of the cell nucleus, a milestone of eukaryotic evolution, remains unclear.

The origin of the eukaryotic nucleus must indeed be a milestone in the development of the cell itself, considering that it is the defining factor that sets eukaryotic cells apart from the other broad category of cells-the prokaryotic cell. The eukaryotic cell is neatly compartmentalized into membrane-bound organelles that perform various functions. Among them, the nucleus houses the genetic material. The other organelles float in what is called the cytoplasm. Prokaryotic cells do not contain such compartmentalization. Bacteria and archaea are prokaryotic cells.

The 2001 hypothesis by Prof Takemura and PJ Bell is based on striking similarities between the eukaryotic cell nucleus and poxviruses: in particular, the property of keeping the genome separate in a compartment. Further similarities were uncovered after the discovery and characterization of a type of large DNA virus called giant virus, which can be up to 2.5 m in diameter and contain DNA encoding information for the production of more than 400 proteins. Independent phylogenetic analyses suggested that genes had been transferred between these viruses and eukaryotic cells as they interacted at various points down the evolutionary road, in a process called lateral gene transfer.

Viruses are packets of DNA or RNA and cannot survive on their own. They must enter a host cell and use that cells machinery to replicate its genetic material, and therefore multiply. As evolution progressed, it appears, viral genetic material became integrated with host genetic material and the properties of both altered.

In 2019, Prof Takemura and his colleagues made another breakthrough discovery: the medusavirus. The medusavirus got its name because, like the mythical monster, it causes encystment in its host; that is, it gives its host cell a hard covering.

Via experiments involving the infection of an amoeba, Prof Takemura and his colleagues found that the medusavirus harbors a full set of histones, which resemble histones in eukaryotes. Histones are proteins that keep DNA strands curled up and packed into the cell nucleus. It also holds a DNA polymerase gene and major capsid protein gene very similar to those of the amoeba. Further, unlike other viruses, it does not construct its own enclosed viral factory in the cytoplasm of the cell within which to replicate its DNA and contains none of the genes required to carry out the replication process. Instead, it occupies the entirety of the host nucleus and uses the host nuclear machinery to replicate.

These features, Prof Takemura argues, indicate that the ancestral medusavirus and its corresponding host proto-eukaryotic cells were involved in lateral gene transfer; the virus acquired DNA synthesis (DNA polymerase) and condensation (histones) genes from its host and the host acquired structural protein (major capsid protein) genes from the virus. Based on additional research evidence, Prof Takemura extends this new hypothesis to several other giant viruses as well.

Thus, Prof Takemura connects the dots between his findings in 2019 and his original hypothesis in 2001, linking them through his and others work in the two decades that come in between. All of it taken together, it becomes clear how the medusavirus is prime evidence of the viral origin of the eukaryotic nucleus.

He says: This new updated hypothesis can profoundly impact the study of eukaryotic cell origins and provide a basis for further discussion on the involvement of viruses in the evolution of the eukaryotic nucleus. Indeed, his work may have unlocked several new possibilities for future research in the field.

Reference: Medusavirus Ancestor in a Proto-Eukaryotic Cell: Updating the Hypothesis for the Viral Origin of the Nucleus by Masaharu Takemura, 3 September 2020, Frontiers in Microbiology.DOI: 10.3389/fmicb.2020.571831

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In Ancient Giant Viruses Lies the Truth: Medusavirus Key to Deciphering Evolutionary Mystery - SciTechDaily

Cell Biology

Neogene Therapeutics Raises $110 Million Series A Financing to Develop Next-Generation Fully Personalized Neo-Antigen T Cell Receptor (TCR) Therapies…

Sept. 14, 2020 12:00 UTC

Series A Financing led by EcoR1 Capital, Jeito Capital and Syncona with continued support of strategic seed investors Vida Ventures, TPG and Two River

Neogenes proprietary technology platform identifies specific T cell receptor (TCR) genes from routine tumor samples using state-of-the-art synthetic biology tools

Co-founded by renowned T cell engineering expert Ton Schumacher, Ph.D. and Carsten Linnemann, Ph.D. with investment from cell therapy industry veteran Arie Belldegrun, M.D. FACS

NEW YORK & AMSTERDAM--(BUSINESS WIRE)-- Neogene Therapeutics, Inc., a pre-clinical stage biotechnology company pioneering a new class of fully personalized neo-antigen T cell therapies to treat cancer, today announced that it has raised $110 million in a Series A financing. The financing was co-led by EcoR1 Capital, Jeito Capital and Syncona, with participation from Polaris Partners and Pontifax. Seed investors Vida Ventures, TPG and Two River also participated in the round.

Neogene, a Two River company, was founded in 2018 by a team of world-class cell therapy experts to advance the development of neo-antigen T cell therapies. Carsten Linnemann, Ph.D., Chief Executive Officer of Neogene, and Ton Schumacher, Ph.D., Principal Investigator at the Netherlands Cancer Institute, Oncode Institute and 2020 recipient of the Dutch Research Councils Stevin Award co-founded the Company with individual investments by cell therapy industry veterans Arie Belldegrun, M.D. FACS, founder of Kite Pharma, Inc. and Co-Founder and Executive Chairman of Allogene Therapeutics, Inc. and David Chang, M.D., Ph.D., Co-Founder, President and Chief Executive Officer of Allogene. Dr. Linnemann and Dr. Schumacher previously co-founded T-Cell Factory B.V., a company acquired by Kite Pharma in 2015.

Dr. Schumacher, an internationally leading immunologist in the areas of neo-antigen biology and T cell engineering, developed the seminal concepts of Neogenes proprietary technology. Neogenes platform allows for the isolation of neo-antigen specific TCR genes from tumor biopsies that are routinely obtained from cancer patients during treatment. The tumor-infiltrating lymphocytes (TIL) obtained by these tumor biopsies frequently express TCRs specific for mutated proteins found in cancer cells (neo-antigens). The Companys proprietary technology uses state-of-the-art DNA sequencing, DNA synthesis and genetic screening tools to identify such neo-antigen specific T cell receptor genes within tumor biopsies with high sensitivity, specificity and at scale. The isolated TCR genes are subsequently engineered into T cells of cancer patients to provide large numbers of potent T cells for therapy.

Neogene is committed to forging a path for new fully personalized engineered T cell therapies in solid cancer that are redirected towards neo-antigens found on cancer cells, said Dr. Linnemann. While engineered T cell therapies have transformed the treatment paradigm for patients with hematologic malignancies, the industry has struggled to translate this success to the enormous unmet need in patients with advanced solid tumors. We believe that through a fully individualized approach using patient-specific TCRs to target neo-antigens, engineered T cell therapy can become broadly accessible to these patients. We are excited that our vision is shared by an outstanding syndicate of marquee investors, who have a deep understanding of and commitment towards the development of novel cell therapies in oncology.

Neo-antigens represent ideal targets for cancer therapy, as they inevitably arise from DNA mutations that enable tumor development in the first place. Further supporting this concept is clear, correlative evidence linking T cell reactivity against neo-antigens with tumor regression in several patients, said Dr. Schumacher. The Neogene platform makes it possible to exploit the neo-antigen reactive TCRs that are present in TIL without a requirement for viable tumor material. In addition, its syn-bio based approach offers major advantages with respect to standardization and scalability and will be critical to achieve our goal of bringing personalized engineered T cell therapies to patients.

In this Series A financing, Neogene expands its distinguished investor base with leading health-care investors from both the U.S. and Europe. For the seed-investors Vida Ventures, TPG and Two River, Neogene marks the second major collaboration in the cell therapy space after the launch of Allogene Therapeutics in 2018. Neogenes seed-financing in 2019 enabled the Company to achieve proof-of-concept for its neo-antigen technology platform and built on the respective expertise of Vida Ventures, Two River and TPG in the gene and cell therapy space.

We believe that Neogenes technology and therapeutic approach has the potential to become a game changer for the treatment of cancer, said Oleg Nodelman, Founder and Managing Director of EcoR1 Capital. We are impressed by the bold vision of the management team and are thrilled to support Neogene as it advances its mission of developing novel therapies for cancer patients in need.

Neogenes approach perfectly aligns with Jeitos mission. Jeito was launched recently to support new and established entrepreneurs aspiring to help patients in need by pioneering novel, ground-breaking medicines underlined by highest quality innovation, said Rafale Tordjman, Founder and Chief Executive Officer at Jeito Capital. We are delighted to welcome Neogene as the first investment into our new portfolio.

We are excited to partner with the outstanding Neogene team, said Martin Murphy, Chief Executive Officer of Syncona. Neogenes technology offers a radically innovative approach to utilize the therapeutic potential of TIL cells by employing state-of-the-art TCR engineering and synthetic biology technologies. Facilitated by the Series A, Neogene intends to further develop its technology with growing offices in Amsterdam and the U.S. with the goal to initiate Phase I clinical studies in 2022.

About Neogene Therapeutics

Neogene Therapeutics, Inc. is a pre-clinical stage biotechnology company pioneering development of next-generation, fully personalized engineered T cells therapies for a broad spectrum of cancers. The Companys engineered T cells target mutated proteins found in cancer cells due to cancer-associated DNA mutations, or neo-antigens, that render tumor cells vulnerable to detection by T cells. Neogenes proprietary technology platform aims to identify TCR genes with specificity for neo-antigens from tumor biopsies. Neogenes novel approach intends to deliver a tailored set of TCR genes for each individual patient, which will be engineered into patient-derived T cells directing them towards neo-antigens in tumor cells, with the goal of providing a fully personalized engineered T cell therapy for cancer.

For more information, please visit http://www.neogene.com, and follow Neogene Therapeutics on LinkedIn.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200914005309/en/

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Neogene Therapeutics Raises $110 Million Series A Financing to Develop Next-Generation Fully Personalized Neo-Antigen T Cell Receptor (TCR) Therapies...

Cell Biology

Feeding off fusion or the immortalization of tumor cell – Biophotonics.World

image illustrating the mitochondrial fusion of the Drosophila tumor cells in red, blue staining showing tumor cell nuclei.

Image source: IMBA

By: Knoblich lab

Worldwide, cancer is the second leading cause of death - in 2018 alone, it claimed approximately 9.6 million lives, or one in six deaths. The development of cancer is incredibly complex and is controlled by an interplay of various factors - only recently, it became clear that the majority of human cancers such as cervical, gastrointestinal and breast among others, originate from adult stem cells becoming deregulated. These adult stem cells are present in many of our organs, where they provide a constant supply of cells to replace old and dead cells. Identifying the mechanisms of how these developmentally tightly regulated stem cells break free from their regulations is an important topic within the scientific community, including the Knoblich lab at IMBA.

One key step in tumorigenesis are the mechanics driving tumor cell initiation, which trigger their fate in becoming tumorigenic. They have, thus far, mainly been studied at gene regulation levels, by researching tumor suppressor genes MYC, p53 or KRAS. Metabolic changes within tumor cells are a well-known characteristic, but whether these are a consequence or the cause of tumor cell immortalization is still not known, and thus the focus of the most recent publication from Knoblich's team.

The researchers chose the fruit fly Drosophila melanogaster as tumor model - this established yet somewhat unconventional model organism boasts a long history in tumor studies, with discoveries in mutations of tumor suppressor genes dating back to the 1970s. Learnings from this simple model organism can then be used as a powerful tool as basis for further studies on human genes. In Drosophila, the scientists visualized the exact timepoint when tumor initiating cells became immortal and manipulated the process genetically - a feat which is not readily accomplished in mammalian tumors, due to their high complexity.

"We used a Drosophila neural stem cell (NSCs) tumor model, which is induced by the depletion of the well-known tumor suppressor called Brat. By using this model, we investigated whether the metabolism plays an active role in Brat tumor cell immortalization. Our findings in Drosophila will then be used as a basis for subsequent studies in human cells and lay the basis for mechanistic studies of human cancers," explains Jrgen Knoblich, IMBA group leader and Scientific Director.

Indeed, the researchers found Brat tumors to be highly oxidative, with higher oxygen consumption rates compared to normal brains. This proved to be quite the surprising discovery, as tumors are widely considered to be glycolytic.

In an additional exciting finding, the scientists from Knoblich's team found that the oxidative metabolism, which is a mitochondrial oxygen-dependent bioenergetic pathway, plays a key role in tumor cell immortalization. "We noticed that during tumor initiation, the mitochondrial membranes are fused. This drastic change in mitochondrial morphology leads to an increase in efficiency in oxidative phosphorylation, which explains why we found increased levels of NAD+ and NADH, two key molecules involved in bioenergetics," explains Franois Bonnay, postdoc in the Knoblich lab and first author of the study.

With additional experiments, the scientists showed that in the Drosophila brain, it is indeed the increased oxidative phosphorylation and NADH/NAD+ metabolism mediated by mitochondrial fusion which is absolutely necessary for tumor initiating cells to become immortal.

"Our findings overturn previous concepts about the biology of these tumors and open up an array of exciting follow up questions, including whether the mechanisms we just discovered in the fruit fly are also applicable to mammalian tumors. Questions we will also strive to answer are, how exactly does the NADH/NAD+ metabolism favour tumor cell immortalization, and does it achieve this via signalling, or through epigenetic changes? We are thrilled to advance our work in this field", says Knoblich.

Source: IMBA -- Institute of Molecular Biotechnology of Austrian Academy of Sciences

Related journal article:http://dx.doi.org/10.1016/j.cell.2020.07.039

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Feeding off fusion or the immortalization of tumor cell - Biophotonics.World

Neuroscience

Neuroscience Students Receive Real Brains Through the Mail – Nerdist

Neuroscience students at Lafayette College inEaston, Pennsylvania are dissecting sheeps brains in their own homes. The students, who are studying from home due to COVID-19, were mailed the brains by the college. Other schools, such as Stanford and the University of Arizona, are also mailing animal organs home to students.

In a Lafayette press release, which comes via Futurism, the college outlines how Luis Schettino, an associate professor of psychology and neuroscience, is teaching his students to dissect the brains at home. The objective of the dissection, Lafayette says, is to impress on students the importance of brain architecture on the control of behaviorin particular, how complex behavior is controlled during human interactions.

More specifically, Schettino aims to teach his class about the role neurobiology plays in the use of force by police officers when arresting minority individuals. The professor notes that By learning the role that brain architecture plays on how humans behave, we become aware of our weaknesses

Schettino and the students are using sheeps brains because they are architecturally similar to peoples. Lafayette notes that sheep-brain structures are in roughly the same place as those of the human brain making them relevant to our own in terms of neurophysiology.

Futurism notes that biology programs at other institutes for higher education are also mailing home organs for study; including everything from eyeballs to entire fetal pigs. Despite the successful transition to at-home dissections, however, at least Schettino seems to miss in-person learning.

Pearson Scott Foresman

To be honest, there is no substitute for having the students be all within the lab where we can communicate more directly Schettino told Futurism. What I mean is that this is, of course, a second-best solution, the professor added.

Moving forward, the second module of the course will involve studying ratshalf of whom will undergo brain lesions of the hippocampusas they navigate mazes. Schettino will upload video of both rat groups as they learn to solve the maze so the students can code the behavior from home.

What do you think about students performing dissections at home? Do you have any issues with colleges and universities sending organs through the mail? Let us know your thoughts in the comments!

Feature image: WB

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Neuroscience Students Receive Real Brains Through the Mail - Nerdist

Neuroscience

Renee Miller: at the crossroads of neuroscience and fantasy sports – Campus Times

Neuroscience and sports journalism arent two fields that usually cross. In fact, the only intersection that seems to exist is Renee Miller, an associate professor of Brain and Cognitive Sciences (BCS) at UR. But merging those fields is just her day job. Shes also an award winning sports writer who has worked at RotoWire, ESPN, and The Athletic.

Millers specialty is applying cognitive science to fantasy sports, especially fantasy football. In fact, she literally wrote the book on the subject, and last year won the Fantasy Sports Writers Associations Best Fantasy Football Series award for her column at The Athletic, Brain Games.

Her book, Cognitive Bias in Fantasy Sports: Is Your Brain Sabotaging Your Team?, and her column focus on the same questions: How do our biases and decision-making processes make us worse at fantasy sports? How do they make us better? How can we apply cognitive science in our daily lives, and how can we become more aware of the way we are already unknowingly doing so?

Fantasy sports interested Miller long before she began writing about them. She describes her family as big sports fans, pointing to her upbringing as where she first got interested.

In an interview with the Campus Times, Miller recalled, [My brother] started a fantasy league with all his friends and needed an extra body, so he got me and my dad involved [] and I loved it.

Since then, Miller has added a few more leagues into the mix, including one full of Neuroscience students. She also has tried out other sports, and a variety of formats.

Miller is particularly a fan of daily fantasy, even advocating on behalf of DraftKings, a major daily fantasy website, when they successfully sought to end New York States ban on daily fantasy betting in 2016.

Daily fantasy involves skill, like poker, Miller said, adding that the fact that skill is involved (and not just random chance) is actually what attracts her to daily fantasy. Im a scientist, and a scientist is a problem solver. I view [daily fantasy] as a puzzle to solve. Its a different puzzle every week. Theres a ton of different possible solutions. I have a great time trying to figure out what are my best three or four.

Miller was into daily fantasy from the beginning around 2010 and fantasy football as a whole only a few years before that. She didnt begin writing until a couple years later when a colleague used fantasy as an example of a place where cognitive bias affects our daily life. That got her thinking about how she could connect her interest in neuroscience to her love of fantasy. Then in 2013, she published a book about it.

That was the beginning of her journey as a sports writer. But she didnt immediately know where to go next. I had a mentor, somebody who was running a fantasy site that I respected [] and he said, What you have to do is start a blog.

So thats exactly what she did. After Millers blog gained popularity, she began writing for RotoWire, ESPN, and The Athletic.

Millers writing is fairly personal despite the focus on science. She isnt reporting on some new study; shes connecting long-established phenomena to something she enjoys, and shes telling us how we can do the same. Shes also seemingly the only person conducting research about sex differences in both the behavior of small worms and professional athletes.

Her tone is that of a knowledgeable friend sharing tips, rather than a scientist sharing test results or an ESPN talk show host giving their hot take. She is often more focused on the best ways to improve your decision-making process than which wide receiver is going to have a good game this week.

[Starting a blog] was very uncomfortable for me at first because Im not a self-promoter, Miller said. I didnt write the book to get rich or famous. At heart Im an educator, and like to share what I know with other people.

As a professor (and the academic advisor for An Nguyen, the CT Publisher) she teaches college students; as a writer she teaches sports fans. But in either position, her goal is more or less the same: sharing her advice, free from condescension, about topics she is passionate about.

You can find links to Millers book and sports writing on her Twitter, @reneemiller01. More information about her work in academia can be found on her UR BCS faculty page here.

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Renee Miller: at the crossroads of neuroscience and fantasy sports - Campus Times

Neuroscience

From neuroscience to bringing Morocco to the Hunter – Breakfast – ABC News

Have you ever considered changing your career?

Dr Ihssane Zouikr is a successful neuroscientistfrom Marrakech,Morocco. He came to Australia to take up a PhD position at the University of Newcastle.

Afterworking in Japan, Dr Zouikr and his family chose to settle in Newcastle where he now runs a retail business which imports arts and crafts from his home country.

He told ABC Newcastles Dan Cox about his journey and change in career.

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From neuroscience to bringing Morocco to the Hunter - Breakfast - ABC News