Category Archives: Cell Biology

The art of science: Olympus launches second global image of the year award – News-Medical.net

Sep 16 2020

Following the success of the first Global Image of the Year Life Science Light Microscopy Award, Olympus has launched its second annual Global Image of the Year Award to recognize the best in life science imaging. Those interested in participating can enter through Jan. 10, 2021 by uploading up to three images, with a description of the equipment used, at Olympus-LifeScience.com/IOTY. Winners will be selected by a jury panel and announced in March 2021.

Prizes include an Olympus SZX7 stereo microscope with a DP27 digital camera for the global winner and an Olympus CX23 upright microscope for the regional winners in Asia, Europe and the Americas.

The jury consists of global representatives from both science and the arts, including Wendy Salmon, a light microscopy specialist at Whitehead Institute for Biomedical Research at MIT; Geoff Williams, the manager of the Leduc BioImaging Facility at Brown University; Harini Sreenivasappa, the microscopy facility manager of the Cell Imaging Center at Drexel University; Safa Shehab, a professor at United Arab Emirates University; Sin Culley, a postdoctoral research associate at the MRC Laboratory for Molecular Cell Biology at UCL; Stefan Terjung, the operational manager of the Advanced Light Microscopy Facility at EMBL Heidelberg; Xiang Yu, a professor in the School of Life Sciences at Peking University and investigator of the Peking-Tsinghua Center for Life Sciences and the McGovern Institute for Brain Research; Graham Wright, the chief technology officer at A*STARs Research Support Centre; and Ikuko Koyama-Honda, the project lecturer of the Graduate School and Faculty of Medicine, the University of Tokyo.

All entries will be evaluated based on artistic and visual aspects, scientific impact and microscope proficiency.

Olympus IOTY Award began in 2017 as the Image of the Year European Life Science Light Microscopy Award with the aim to celebrate both the artistic and scientific value of microscopy images. Today, the competition stays true to this mission by encouraging people across the world to look at scientific images in a new way, appreciate their beauty and share images with others.

More information about the Global Image of the Year Life Science Light Microscopy Award, including jury members biographies, last years winning images and the full terms and conditions, can be found at Olympus-LifeScience.com/IOTY.

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The art of science: Olympus launches second global image of the year award - News-Medical.net

Beyond the bench: how inclusion and exclusion make us the scientists we are – DocWire News

This article was originally published here

Mol Biol Cell. 2020 Sep 15;31(20):2164-2167. doi: 10.1091/mbc.E20-06-0374.

ABSTRACT

Recent events encompassing social injustices, healthcare disparities, and police brutality against Black citizens highlight the continued need to strive toward unbiased and inclusive practices in all realms of the world. Our voices as cell biologists are powerful tools that can be used to combat inequities in the scientific landscape. In this inaugural Voices essay, we discuss how exclusion and inclusion events have contributed to our scientific journeys and how scientists can work to create an inclusive environment for our trainees and colleagues. As underrepresented minority scientists in the early and late stages of our scientific training, we frame the trainee experience to provide insight from unique perspectives. This essay also provides actionable items that the cell biology community can implement to promote inclusivity. We anticipate that initiating an open dialogue focused on diversity and inclusion will promote growth in the field of cell biology and enable scientists to assess and assume their role in creating welcoming environments. We believe that scientists at all stages in their careers can make meaningful and habitual contributions to supporting inclusivity in cell biology, thereby creating a future where diversity, equity, and inclusion are expected, not requested.

PMID:32924843 | DOI:10.1091/mbc.E20-06-0374

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Beyond the bench: how inclusion and exclusion make us the scientists we are - DocWire News

A cell culture master class: What your cells wish they could tell you – Science Magazine

Cell culturethe controlled growing of cells outside their natural environmentmay be commonplace in molecular biology laboratories, but one thing that strikes fear in both novices and experts using these techniques is contamination. Whether it occurs via chemicals (impurities in media, sera, and water) or biological components (bacteria, viruses, and mycoplasma), contamination can bring research to a halt, wasting both time and money and possibly raising doubts about the validity of a laboratorys findings. Studies have shown that up to 30% of animal cell cultures are contaminated by either microorganisms or other cells.While no researcher is immune to this common problem, an introduction to and/or refresher on good aseptic techniques can help reduce the occurrence of contamination and possibly its severity. This webinar will be a master class for all those who perform primary and immortalized cell culture. It will discuss best practices and common pitfalls, with a special section dedicated to the dangers of contamination and ways to avoid it. An additional section will be devoted to protein expression in suspension. This webinar should be equally beneficial to both novices and experts in cell culture.

During the webinar, the speakers will:

This webinar will last for approximately 60 minutes.

Johns Hopkins School of MedicineBaltimore, MD

Stowers Medical InstituteKansas City, MO

Dr. Zhao, originally from Henan Province, China, graduated from Zhengzhou University with an M.D. degree. She earned her Ph.D. in veterinary pathobiology from the University of Missouri-Columbia, then completed a 2-year certification in science management at the University of Kansas. In 2012 she joined the Stowers Institute of Medical Research in Kansas City, Missouri, as a research coordinator. In 2019, she was promoted to head of Tissue Culture at Stowers and in 2020 was named head of Tissue Culture and Media Prep. With 15 years of experience in cell culture, including 3D organoid culture, primary cell culture, virus work, and gene editing, Dr. Zhao collaborates with Stowers researchers to develop new products and technologies in the cell-culture field.

Science/AAASWashington, DC

Dr. Oberst did her undergraduate training at the University of Maryland, College Park, and her Ph.D. in Tumor Biology at Georgetown University, Washington D.C. She combined her interests in science and writing by pursuing an M.A. in Journalism from the Philip Merrill College of Journalism at the University of Maryland, College Park. Dr. Oberst joined Science/AAAS in 2016 as the Assistant Editor for Custom Publishing. Before then she worked at Nature magazine, the Howard Hughes Medical Institute, The Endocrine Society, and the National Institutes of Mental Health.

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A cell culture master class: What your cells wish they could tell you - Science Magazine

S2 Genomics Announces Asia-Pacific Distribution Partnerships for the Singulator 100 System With SCRUM, PharmiGene, LnCBio, Thunderbio Science, and…

S2 Genomics, Inc., today announced that it has entered into distribution agreements with SCRUM, PharmiGene, LnCBio, Thunderbio Science, and TrendBio for the promotion, sales, and support of S2s Singulator 100 System and associated products for single-cell genomics and cell biology applications in the Asia-Pacific region.

The distribution agreements cover Japan (SCRUM), South Korea (LnCBio and Thunderbio Science), Taiwan (PharmiGene), and Australia and New Zealand (TrendBio).

The Asia-Pacific region is experiencing significant growth in single-cell genomic and cell biology analyses, and that is driving a need for improved sample preparation solutions, said Dr. Stevan Jovanovich, S2 Genomics Chief Executive Officer. We are excited to welcome SCRUM, PharmiGene, LnCBio, Thunderbio Science, and TrendBio as key partners for S2 Genomics. Each of these distributors has significant expertise in life sciences, and especially in genomics. Expanding our commercialization efforts into the Asia-Pacific region represents a significant milestone for S2 Genomics.

S2 Genomics Singulator 100 system enables consistent isolation of single cells or nuclei from solid tissue samples, essential to producing high-quality single-cell data from difficult tissue types. The Singulator 100 system uses single-use disposable cartridges and proprietary reagents to automate tissue dissociation in a convenient workflow. In addition, the system allows users to create their own dissociation protocols, use their own reagents, and dissociate tissue at low temperature to minimize changes to cell transcriptomes.

Takemitsu Furuta, President and CEO of SCRUM noted, Its exciting for SCRUM to be working with S2 and expand our product portfolio in cell biology, especially single cell genomics. This is also an important area of current life science studies in Japan. I strongly believe the value of this platform will facilitate our customers research studies and greatly improve their experimental efficiency.

S2 Genomics distributor information can be found at http://www.S2Genomics.com/distributors.

About S2 Genomics, Inc.

S2 Genomics, founded in 2016, is a leading developer of laboratory automation solutions for processing solid tissues for single-cell applications. S2 Genomics technology platforms integrate advanced fluidics, optics, and biochemistry to produce automated sample preparation solutions for single-cell sequencing and cell biology markets, enabling discovery and innovation in life science research, healthcare, and agriculture. For more information, visit https://S2Genomics.com.

For Research Use Only. Not for use in diagnostic procedures.

S2 Genomics, the S2 Genomics logo, and Singulator are trademarks of S2 Genomics, Inc.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200909005030/en/

Dr. John Bashkin, VP Business Development, S2 Genomics, Inquiries@s2genomics.com

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S2 Genomics Announces Asia-Pacific Distribution Partnerships for the Singulator 100 System With SCRUM, PharmiGene, LnCBio, Thunderbio Science, and...

10x Genomics First to Market With Product to Simultaneously Capture Epigenome and TranscriptomeChromium Single Cell Multiome ATAC + Gene Expression…

PLEASANTON, Calif., Sept. 15, 2020 (GLOBE NEWSWIRE) --10x Genomics (Nasdaq: TXG) today announced it has begun shipping its Chromium Single Cell Multiome ATAC + Gene Expression solution to customers, marking the first commercial release of a product capable of simultaneously profiling the epigenome and transcriptome from the same single cell. This multi-omic approach provides customers with the ability to link a cells epigenetic program to its transcriptional output, enabling a better understanding of cell functionality and bypassing the need to infer relationships through computer simulations.

This is one of our most ambitious undertakings at the company, said Ben Hindson, co-founder and Chief Scientific Officer of 10x Genomics. By introducing the first solution that captures ATAC and gene expression simultaneously, researchers can gain even more clarity by combining two already powerful methods to profile biological systems at single cell resolution simultaneously for the first time.

The new solution builds on an array of new products launched by the company this year for both its Chromium platform for single cell analysis as well as its Visium platform for spatial genomics. Early customers already working with Chromium Single Cell Multiome ATAC + Gene Expression include Stanford University School of Medicine, Icahn School of Medicine at Mt. Sinai and Spains Centro Nacional de Anlisis Genmico.

My lab is interested in understanding why some immune cell types fail to fight the cancer, said Dr. Ansuman Satpathy, Assistant Professor of Pathology, Stanford University School of Medicine. We plan to use 10x Genomics' new assay to understand the epigenetic and transcriptional regulation of immune cell dysfunction directly in patient samples, and to use this information to precisely engineer more effective immunotherapies in the future.

Until now, we have relied on computational prediction to match a cell's epigenome to a single-cell gene expression profile, said Dr. Holger Heyn, leader of the single cell genomics team at Spains Centro Nacional de Anlisis Genmico that is working on delineating the dynamics underlying B-cell differentiation and activation. 10x Genomics new multiome assay will allow us to directly measure what before could only be predicted, and offers a new gold standard that will confirm how accurate these predictions had been.

"With this new technology, we can better understand the mechanisms affected by the non-coding risk genetic variation across a wide range of neuropsychiatric diseases, including Alzheimers, Parkinsons, Schizophrenia, bipolar disorder and major depression, along with different severity of neuropathology and clinical symptomatology," added Dr. Panagiotis Roussos, Associate Professor of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai.

By using Chromium Single Cell Multiome ATAC + Gene Expression, researchers can:

Chromium Single Cell Multiome ATAC + Gene Expression is shipping to customers. To learn more, visit https://www.10xgenomics.com/products/single-cell-multiome-atac-plus-gene-expression.

About 10x Genomics10x Genomics is a life science technology company building products to interrogate, understand and master biology to advance human health. The companys integrated solutions include instruments, consumables and software for analyzing biological systems at a resolution and scale that matches the complexity of biology. 10x Genomics products have been adopted by researchers around the world including 97 of the top 100 global research institutions and 19 of the top 20 global pharmaceutical companies, and have been cited in over 1,500 research papers on discoveries ranging from oncology to immunology and neuroscience. The companys patent portfolio comprises more than 775 issued patents and patent applications.

Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 as contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements generally can be identified by the use of forward-looking terminology such as may, will, should, expect, plan, anticipate, could, intend, target, project contemplate, believe, estimate, predict, potential or continue or the negatives of these terms or variations of them or similar terminology. These forward-looking statements include statements regarding 10x Genomics, Inc.s partnership activities, which involve risks and uncertainties that could cause 10x Genomics, Inc.s actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on managements current expectations, forecasts, beliefs, assumptions and information currently available to management, and actual outcomes and results could differ materially from these statements due to a number of factors. These and additional risks and uncertainties that could affect 10x Genomics, Inc.s financial and operating results and cause actual results to differ materially from those indicated by the forward-looking statements made in this press release include those discussed under the captions "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" and elsewhere in the documents 10x Genomics, Inc. files with the Securities and Exchange Commission from time to time. The forward-looking statements in this press release are based on information available to 10x Genomics, Inc. as of the date hereof, and 10x Genomics, Inc. disclaims any obligation to update any forward-looking statements provided to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as required by law. These forward-looking statements should not be relied upon as representing 10x Genomics, Inc.s views as of any date subsequent to the date of this press release.

Disclosure Information10x Genomics uses filings with the Securities and Exchange Commission, its website (www.10xgenomics.com), press releases, public conference calls, public webcasts and its social media accounts as means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD.

ContactsMedia:media@10xgenomics.comInvestors:investors@10xgenomics.com

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10x Genomics First to Market With Product to Simultaneously Capture Epigenome and TranscriptomeChromium Single Cell Multiome ATAC + Gene Expression...

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

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

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

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

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...