Category Archives: Cell Biology

2019 Was Big for Academic Publishing. Heres Our Year in Review – The Scientist

The global push to make the scholarly literature open access continued in 2019. Some publishers and libraries forged new licensing deals, while in other cases contract negotiations came to halt, and a radical open access plan made some adjustments. Here are some of the most notable developments in the publishing world in 2019:

This year, The Scientist heard scientists complaints about the supplementary files that accompany journal articles and concerns about predatory journals on PubMed, the massive repository of abstracts and citations belonging to the US National Library of Medicine (NLM).

The NLM has quality control procedures for PubMed in place, but some articles have slipped through the cracks. Academics began raising concerns about the presence of predatory journals on PubMed for several yearsand those worries remain today.

Supplementary files, on the other hand, have been criticized by scientists for containing broken hyperlinks and being published in clunky and outdated formats. As a result, more scientists are opting to deposit their files into online repositories hosted by universities, research institutions, and companies. Publishers, too, have begun to encourage this practice.

New tools can have their own flaws. This summer, several scientists noted that their papers were erroneously flagged by journals automatic plagiarism detectors. Instead of identifying actual cases of plagiarism, they were picking out author lists, methods, or references. Despite some of the current limitations of this technology, some publishers are working on extending the reach of artificial intelligence into other parts of the peer-review process, such as identifying statistical issues. These will turn out to be useful editorial tools, Bernd Pulverer, chief editor of The EMBO Journal, told The Scientistin June. But [they] most certainly should not replace an informed expert editorial assessment, let alone expert peer review.

At the end of February, contract negotiations between Elsevier and the University of California (UC) came to a halt. The two sides had failed to agree on terms after more than half a year of discussions. The previous contract ended in December 2018, but Elsevier continued to provide free access until July. Since then, UC has been unable to read new content published in Elseviers journals.

Our commitment hasnt wavered, and our faculty has continued to tell us we should be standing firm.

Jeffrey MacKie-Mason, University of California, Berkeley

In August, UC faculty members protested Elsevier by stepping down from the editorial boards of Cell Press journals, which include some of publishers most prestigious titles such as Cell, Neuron,and Current Biology. More than 30 professors signed an open letter stating that they would not return to their posts until a deal between UC and Elsevier was made.

Like Project DEAL, a consortium that represents approximately 700 academic institutions in Germany, UC has been pushing for a contract that combines subscriptions to read paywalled journals and publishing in open-access formats into a single fee. Project DEAL is also currently in a standstill with Elsevier, and hundreds of German institutions have let their subscriptions with the publisher lapse since 2016.

From the very beginning, we said that cost reduction, or at least cost containment, and full open access were the essential elements, Jeffrey MacKie-Mason, the university librarian at the University of California, Berkeley, and the co-chair of UCs negotiation task force, told The Scientistearlier this month. Our commitment hasnt wavered, and our faculty has continued to tell us we should be standing firm.

Other publishers have also faced difficult negotiations. This week, swissuniversities, an organization that represents universities in Switzerland, announced that they would no longer have a contract with Springer Nature starting in January 2020 due to a failure to come to a new licensing agreement.

In January, Wiley and Project DEAL announced that they had successfully forged a new licensing agreement. The deal allows member institutions to access paywalled papers and publish open-access articles for a single annual fee that is determined by the total number of published manuscripts. With Wiley, we found a publisher on the other side of the table that was willing to make this transition [to open access] in partnership with us, Gerard Meijer, a molecular physicist at the Fritz Haber Institute of the Max Planck Society and a member of the DEAL negotiations team, told The Scientistin March.

Wiley subsequently announced deals with open-access elements (which are often called transformative deals) with consortia of research institutions in Norway and Hungary, where negotiations with Elsevier had also come to a standstill. Unlike the DEAL contract, however, these agreements included fixed fees and a specified number of articles that could be published open access per year.

In the months since, Elsevier has managed to turn the tide in Norway and Hungary, where it now has transformative deals in place. The publisher also recently forged such an agreement with the Bibsam consortium, which represents academic institutions in Sweden. Bibsam had previously terminated its negotiations with Elsevier and let their contracts lapse in mid-2018. I think Elsevier has become more flexible during the last couple of months, Wilhelm Widmark, the library director at Stockholm University and a member of the steering committee for the Bibsam consortium, told The Scientistthis month.

Elsevier has also made transformative deals with both individual universities and library consortia in several other countries. Many other publishers, including Springer Nature, Cambridge University Press, and Frontiers, have also forged new transformative deals this year.

Last year, a group of European funding agencies calling themselves cOAlition S launched a radical plan to put an end to paywalled journals. The initiative, dubbed Plan S, mandated that academics receiving grants from participating funders must publish solely in open-access journals starting in 2020. The plan also highlighted 10 key principles, which included funders commitments to assist with publication fees and sanctions for those who broke the new rules.

Since the plans debut, several other national and charitable agencies around the world, including the Bill and Melinda Gates Foundation in the US, the World Health Organization, and Jordans Higher Council for Science and Technology, joined the coalition.

Plan S has been met with mixed reactions. Although many researchers have praised the open-access mandates, the initiative has been criticized by both publishers and members of the academic community. One of the key concerns was a ban on hybrid journals, which contain both open-access and paywalled articles and include titles such as Cell, Science, and The Lancet.

In response, cOAlition S has since relaxed its initial guidelines. The updated rules, which were published in May, include a temporary reversal of a proposed cap on article processing fees (payments for publishing open-access articles) and a softened stance on hybrid journalsthey will now be allowed for a limited time if they are a part of a transformative agreement. The group also postponed the deadline for implementing its rules from 2020 to 2021 to give publishers and academics more time to prepare for the changes.

Other notable developments in publishing this year include: a $50 million fine for OMICS International, a publisher and conference organizer accused of predatory behavior, a call from academics to drop statistical significance, and a new preprint server for clinical research.

Diana Kwon is a Berlin-based freelance journalist. Follow her on Twitter@DianaMKwon.

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2019 Was Big for Academic Publishing. Heres Our Year in Review - The Scientist

Global Transmission Electron Microscope Market 2019 Industry Statistics on Key Trends, Market Status, and Opportunities to 2025 – Market Reports…

Global Transmission Electron Microscope Market Professional Survey Report 2019

This report studies the Transmission Electron Microscope market with many aspects of the industry like the market size, market status, market trends and forecast, the report also provides brief information of the competitors and the specific growth opportunities with key market drivers. Find the complete Transmission Electron Microscope market analysis segmented by companies, region, type and applications in the report.

If you are looking for a thorough analysis of the competition in the global Transmission Electron Microscope market, then this report will definitely help you by offering the right analysis. Under the competitive analysis section, the report sheds light on key strategies, future development plans, product portfolios, and other aspects of the business of prominent players. Main players are evaluated on the basis of their gross margin, price, sales, revenue, business, products, and other company details.

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Transmission electron microscopy (TEM) is an imaging technology in which electron beams pass through very thinly sectioned specimens. As the electrons are transmitted through the specimen and interact with its structure, an image resolves that is magnified and focused onto an imaging medium, such as photographic film or a fluorescent screen, or captured by a special CCD camera. Because the electrons used in transmission electron microscopy have a very small wavelength, TEMs can image at much higher resolutions than conventional optical microscopes that depend on light beams. Due to their higher resolving power, TEMs play an important role in the fields of virology, cancer research, the study of materials, and in microelectronics research and development.

Transmission electron microscope market has been growing at a steady pace, owing to its growing demand in healthcare research. This microscope provides high magnifications and high resolution images, which are highly regarded in identifying various microorganisms and cell structure. They are also utilized for molecular and cellular biology. Additionally, growing demand in materials science has also been positively impacting the growth of the market. There is a growing demand for developing lighter and stronger metals, for utilization in body of vehicles, energy production and machineries among others. Such demand has led to higher application of transmission electron microscopes, as it allows for higher visibility of structure and composition of the newly developed material. It also allows for viewing of any possible defects in the structure. Such applications have been promoting the growth of the market. However, these microscopes require the specimen to be thin enough for allowing electrons to pass through. Such specimen preparation difficulties have been hindering the growth of the market for transmission electron microscopes. Increasing application of transmission electron microscopes in semiconductor research and mining sectors are expected to offer good growth opportunities during the forecast period.

Transmission Electron Microscope in its database, which provides an expert and in-depth analysis of key business trends and future market development prospects, key drivers and restraints, profiles of major market players, segmentation and forecasting. A Transmission Electron Microscope Market provides an extensive view of size; trends and shape have been developed in this report to identify factors that will exhibit a significant impact in boosting the sales of Transmission Electron Microscope Market in the near future.

This report focuses on the global Transmission Electron Microscope status, future forecast, growth opportunity, key market and key players. The study objectives are to present the Transmission Electron Microscope development in North America, Europe, China, Japan, Southeast Asia, India and Central & South America.

The following manufacturers are covered: FEI, JEOL, Hitachi, Delong America

Market segment by Type, the product can be split into

Market segment by Application, split into

The Key Offering By This Report:

Table of Contents:

Global Transmission Electron Microscope Market Professional Survey Report 2019

Chapter One: Industry Overview of Transmission Electron Microscope

Chapter Two: Manufacturing Cost Structure Analysis

Chapter Three: Development and Manufacturing Plants Analysis of Transmission Electron Microscope

Chapter Four: Key Figures of Major Manufacturers

Chapter Five: Transmission Electron Microscope Regional Market Analysis

Chapter Six: Transmission Electron Microscope Segment Market Analysis (by Type)

Chapter Seven: Transmission Electron Microscope Segment Market Analysis (by Application)

Chapter Eight: Transmission Electron Microscope Major Manufacturers Analysis

Chapter Nine: Development Trend of Analysis of Transmission Electron Microscope Market

Chapter Ten: Marketing Channel

Chapter Eleven: Conclusion

Chapter Twelve: Appendix

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Top Technical Advances of 2019 – The Scientist

Artificial intelligence tackles life science

Look under the hood of many of this years headline-making discoveries in biology and youll find machine learning, a tool thats gaining ground in the life sciences thanks to growing computational power and the availability of big datasets needed for training. Among other advances in 2019, researchers reported successfully using machine learning to screen images for signs of cancer or infection by pathogens, and to identify epigenetic markers in blood samples that are associated with vascular complications in people with diabetes. Check out our special issue on AI for more examples of how the tool is transforming biology.

Even as computers take on more of the tasks once done by hand, engineers are exploring DNAs capacity to adopt a function usually associated with machines: information storage. This summer, researchers in Boston reported a way of harnessing DNA, together with CRISPR-like base editing machinery, to make a record of events inside living cells that can then be decoded via sequencing. Study coauthor Timothy Lu of MIT told The Scientist that its potential applications include detecting environmental toxins and recording developmental processes.

Another creative spin on CRISPR-Cas9 editing to come out this year is a detection device for particular DNA sequences. Here, the Cas9 enzyme is bound to an RNA and to a graphene chip and engineered not to make cuts in DNA. If the RNA-Cas9 complex connects to its target DNA sequence, it causes a change in the chips electric field and thus a positive readout. The chips developers suggest it could one day be used for quick DNA tests in clinical settings.

Among the endless variations of CRISPR scientists are engineering, one developed this year purports to reduce its off-target effects by avoiding double-strand DNA breaks. The technique, known as prime editing, uses the same Cas9 nuclease as frequently deployed in the CRISPR system but combines the enzyme with a guide RNA called pegRNA and a reverse transcriptase that initiates the addition of a new sequence or base into the genome. Once the new genetic material is incorporated into a cut strand of DNA, the prime editor nicks the unedited strand, signaling to the cell to rebuild it to match the edited strand.

As some researchers worked on their own variations of genome editing, others made an important edit of a recipe for induced pluripotent stem cells. First published by Shinya Yamanaka (now of Kyoto University) in 2006, the method overexpresses genes for four transcription factors in differentiated cells to reset them to a pluripotent state, creating what are known as induced pluripotent stem cells (iPSCs). The most important of the four overproduced factors was thought to be Oct4. But last month, researchers at the Max Planck Institute for Molecular Biomedicine announced theyd not only managed to make mouse iPSCs without tweaking Oct4 levels, but that the process was more efficient that way. If this works in adult human cells, it will be a huge advantage for the clinical applications of iPS cells, Yamanaka wrote in an email to The Scientist.

Shawna Williams is a senior editor atThe Scientist. Email her at swilliams@the-scientist.com or follow her on Twitter @coloradan.

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Top Technical Advances of 2019 - The Scientist

New ‘fishing’ technique to detect thousands of proteins – News-Medical.net

A new study published today in the journal Nature Cell Biology reports the use of a novel fishing method, under microscopy, to pick up thousands of proteins that are involved in supervising how the cell skeleton is assembled.

The scientists used as baits certain to pick up the proteins they were in search of from within the human cells in culture in their laboratory. Their catch using 56 types of baits was an amazing 9,000-plus proteins that attach to Rho family proteins.

The Rho proteins were discovered in the 1990s and became famous in being the managers of the cytoskeletal building process. The 20 human Rho proteins are GTPases, enzymes that operate by splitting the energy-storing molecule GTP. They are found all over the inner aspect of the cell membranes. When activated by a signal from outside or inside the cell, they come on to trigger other protein cascades, that in turn stimulate the remodeling of the cell skeleton, by either adding or removing bits according to the framework desired.

Three Rho proteins have been uncovered in detail so far. These are the Cdc42, Rac1 and RhoA. The first is the protein that determines the path of blood cells migrating towards an infected locus. Rac1 is the protein that triggers the cellular apparatus responsible for pushing a cell (other than a muscle cell) forward. RhoA activates the process of forming fibers that aggregate to either pull in a cells walls or cause tissues to form a resistant mass, as for instance the fibers that form a blood vessels wall.

There are many other proteins in this family, however, and they link up with thousands of others to complete various processes. It was formerly thought that other proteins which bore close similarity to the three listed above would share their function. However, this was later found to be not the case. Instead, variations in the C-terminal ends caused by signal-dependent modifications, and in the cellular organelles they target, cause the biological activity to be quite different from the non-modified forms. It was to explore this area that the current study was begun.

HeLa cell expressing the proximity interaction probe BirA*-Flag-active RAC1. Actin filaments are in green and biotinylated proteins are in magenta. Image Credit: Amlie Robert (IRCM)

The scientists focused on identifying the molecules that interacted with the Rho family of proteins in a proximity interaction network. The Rho proteins are regulated by guanine nucleotide exchange factors (RhoGEFs) and GTPase-activating proteins (RhoGAPs), that switch them on and off as required to bind to the effector molecules.

The scientists used molecules that forced cells in culture to form two-headed proteins. One head consisted of one side of a Rho protein while the other was a biotin ligase enzyme, which attracts other proteins in the vicinity to label them with a biotin moiety using the Rho protein. This process is called proximity-dependent biotinylation. There were 28 of these two-headed proteins.

They also used GTPase enzymes in both active and inactive switch positions. These molecules regulate a host of cellular pathways. The combination of the bait proteins and the GTPases in different configurations enabled the researchers to snag well over 9,000 proteins.

The labeled proteins were then identified singly. To do this, the cells were torn up to release the proteins for analysis. While some of the proteins had already been characterized, such as those which switch the GTPases on and off, there were a multiplicity of other proteins that remained to be defined.

Among those discovered was the protein that connected different parts of the Rho-dependent cytoskeletal assembly first noticed in the 1990s. The RhoA protein was known to cause another protein called ERM to become activated, causing a type of phosphorylation which in turn made the cytoskeleton more stable. But nobody knew how the ERM protein was activated via RhoA interaction. The current work showed that a protein called SLK connects the RhoA to the ERM protein.

Other unfamiliar proteins dredged up in the current study include GARRE and PLEKHG3. These were found to bind to active Rac1 and RhoG respectively. However, the researchers dont know exactly how these complexes function.

To find out more about them, the current study described the other molecules they found during their work so that other laboratories can characterize them and help to reveal their role.

The scientists have not only shown how RhoA-ERM signaling works but demonstrated a unique but successful way to catch a whole lot of proteins. The next step for them is to use this technique to help study how Ras family protein switches function. The Ras superfamily of GTPases, which lies at the heart of multiple cancer pathways is the protein group of which Rho GTPases form a subfamily.

Journal reference:

Bagci, H., Sriskandarajah, N., Robert, A. et al. Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nat Cell Biol (2019) doi:10.1038/s41556-019-0438-7, https://www.nature.com/articles/s41556-019-0438-7

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New 'fishing' technique to detect thousands of proteins - News-Medical.net

Research Fellow in Vascular Stem Cell Biology job with QUEENS UNIVERSITY BELFAST | 190420 – Times Higher Education (THE)

Application closing date 02/01/2020 Salary 33,797 - 40,322 per annum Job category/type ResearchAttachments

Job description

Queen's University Belfast is a driver of innovation based on our talented, multinational workforce. Throughout the University, our academics are collaborating across disciplines to develop new discoveries and insights, working with outside agencies and institutions on projects of international significance. We are connected and networked withstrategic partnerships across the world, helping us to expand our impact on wider society locally, nationally and globally. The University is committed to attracting, retaining and developing the best global talent within an environment that enables them to realise their full potential.

We are a leader in gender equality and diversity, and are one of the UK's most successful universities in the Athena SWAN initiative which promotes gender equality and career progression. The School of MDBS holds an Athena SWAN Silver award in recognition of our commitment and success in addressing gender equality, representation, progression and success for all our staff. We are ranked 1st in the UK for knowledge transfer partnerships, (Innovate UK) 9th in the UK for University facilities (Times Higher Education Student Experience Survey 2018) and 14th in the UK for research quality (Times and Sunday Times Good University Guide 2019).

Based in Belfast, a modern capital city, our beautiful campus is surrounded by abundant acres of parkland and is renowned as one of the safest and affordable cities in the UK. The choice of local Schools from pre-nursery upwards are some of the best available, and lovers of the outdoors can enjoy any number of activities from rowing and kayaking to top class golf among many others. We are immensely proud of what our city and our University will offer you.

Our five core values - Integrity, Connected, Ambition, Respect, Excellence - are shared by our staff and students, representing the expectations we have for ourselves and each other, guiding our day-to-day decisions and the way we behave as individuals in an international organisation.

The Wellcome Wolfson Institute for Experimental Medicine (WWIEM) is an interdisciplinary research centre which is committed to the highest quality scientific endeavour, with over 250 basic and clinical scientists working on site.Our mission is to understand the mechanisms of disease and use that understanding to develop innovative new treatments and therapies to improve patient outcomes.

We are recruiting for a Research Fellow to join the Vascular Stem Cell Biology Research team within the WWIEM led by Prof Alan Stitt to work on a project funded by the British Heart Foundation (BHF). The project will employ in in vitro and in vivo model systems and cell and molecular biological approaches to investigate the regulation of metabolism in vascular progenitors to improve tissue regeneration in ischaemic disease. The successful candidate will design, develop and refine experimental models to investigate vascular repair and re-perfusion of ischaemic tissues in order to obtain reliable and reproducible data.

The successful candidate must:

Candidate Information

Informal enquiries may be directed to Dr Christina O'Neilll via email:christina.oneill@qub.ac.uk

About the GroupFurther Information about the InstituteFurther Information for International ApplicantsNote to EAA Applicants on Brexit

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Research Fellow in Vascular Stem Cell Biology job with QUEENS UNIVERSITY BELFAST | 190420 - Times Higher Education (THE)

Biological Imaging Reagents Market is Expected to Create New Opportunities By 2027 – Market Research Sheets

Transparency Market Research has published a new report on the biological imaging reagents market for the forecast period of20192027. According to the report, the globalbiological imaging reagents marketwas valued at ~US$ 13.5 Bnin2018and is projected to expand at a CAGR of8.5%from2019to2027.

Global Biological Imaging Reagents Market:Overview

Biological imaging reagents are substances used in research and diagnosis purposes in imaging modalities, to enhance THE visualization of internal organs and in vivo live cell imaging. These reagents are used in different imaging modalities such as X-ray, MRI, and ultrasound for THE diagnosis of different diseases, as well as in drug discovery.

Growth of the global biological imaging reagents market can be attributed to the rise in the demand for diagnostic imaging procedures across the globe. Asia Pacific is a highly lucrative market for biological imaging reagents, due to the improving healthcare infrastructure and increase in the geriatric population. North America dominated the global biological imaging reagents market in2018,and the trend is projected to continue during the forecast period, due to the higher prevalence of diseases and high number of imaging procedures.

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High Prevalence and Increase in Incidence Rate of Chronic Diseases to Drive Market

The prevalence of chronic diseases has increased in the past few years across the globe. These diseases include cardiovascular diseases, cancer, diabetes, and neurological disorders.

These diseases need diagnostic imaging tests. Life science reagents such as biological imaging reagents are an integral part of a large number of diagnostic imaging tests. Hence, the high prevalence of these chronic diseases and increasing research activities to discover treatments for these diseases are propelling the global biological imaging reagents market. According to WHO, cardiovascular diseases account for around17.9 milliondeaths globally every year, which constitutes an estimated31%of all deaths.

Rise in the number of diagnostic imaging procedures and increase in research activities for new drug development are the other factors driving the global market. Moreover, the launch of new imaging reagents and approval of products for specific indications in the past few years contributed to the growth of the global biological imaging reagents market.

Nuclear Reagents to be Lucrative Option

Based on class, the global biological imaging reagents market has been classified into contrast reagents, optical reagents, and nuclear reagents. The optical reagents segment dominated the global biological imaging reagents market in2018. However, the contrast reagents segment is anticipated to dominate the global market from2019to2027.

Nuclear reagents are expected to be a highly lucrative segment during the forecast period, owing to the better visualization effects of imaging achieved by these reagents and rise in the demand for radiopharmaceutical agents in imaging modalities

Optical Imaging Dominated Global Market

In terms of modality, the global biological imaging reagents market has been categorized into MRI, ultrasound, X-ray & CT, nuclear, optical imaging, and others. The nuclear segment has been bifurcated into PET and SPECT. The optical imaging segment dominated the global biological imaging reagents market in2018, owing to advanced technologies in optical imaging and large number of research activities on this method.

In-vivo to be Promising Application

Based on application, the global biological imaging reagents market has been bifurcated into in vitro and in vivo.The in vitro segment has been classified into proteomics, genomics, and cell biology. In vivo is likely to be a highly promising segment in the next few years, owing to an increase in vivo research activities by CROs for drug discovery, and growth of the biopharmaceutical industry.

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Life Science Companies to be Lucrative End Users

In terms of end user, the global biological imaging reagents market has been divided into diagnostic laboratories, imaging centers, life sciences companies, academic & research institutes, and others. Life science companies are projected to be a highly lucrative segment during the forecast period. The segment is anticipated to expand at a high CAGR from2019to2027. Increase in the research on new drugs & molecules and large number of collaborations between pharmaceutical companies and CROs are the major factors fueling the growth of the life science companies segment.

Competitive Landscape

Bayer AG, Thermo Fisher Scientific, Inc., PerkinElmer, Inc., and Guerbet are the leading players in the global biological imaging reagents market.

The global biological imaging reagents market is fragmented in terms of number of players. Key players in the global market includeBayer AG, Thermo Fisher Scientific, Inc., PerkinElmer, Inc., Guerbet, Lantheus Holdings, Inc., Bracco S.p.A., GE Healthcare, Becton, Dickinson and Company, Siemens Healthineers, and Luminex Corporation.

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Biological Imaging Reagents Market is Expected to Create New Opportunities By 2027 - Market Research Sheets

Did Cellectis Just Provide a Glimpse of the Future of Cellular Medicine? – The Motley Fool

For all of the wondrous potential of immunotherapies, there have been some notable obstacles in the early goings. Engineering immune cells to attack cancerous tumors can lead to solid results shortly after administering a dose, but for many patients the effects wear off once rapidly mutating tumor cells acquire new defense mechanisms.

Cellectis (NASDAQ:CLLS) thinks it may have a partial solution. In mid-November, the gene editing company published the results from a proof of concept study for its "smart" immunotherapy approach. Is the technique the future of cellular medicine?

Image source: Getty Images.

Today, cellular oncology therapies genetically engineer immune cells to bolster their safety and efficacy as a cancer treatment. There are T cells, natural killer (NK) cells, tumor infiltrating lymphocytes (TILs), and others. They're often engineered with chimeric antigen receptors (CARs) or T cell receptors (TCRs), which allow them to home in on and suppress specific genes in cancer cells.

While current-generation CAR T cells or CAR NK cells are capable of mounting formidable attacks on tumors at first, treatment responses aren't durable for all patients. That's because cancer cells mutate to rely on different proliferation genes, or secrete new molecules into the tumor microenvironment that neutralize immune cells. Meanwhile, overstimulating the immune system can reduce the potency of immune cells and lead to devastating side effects, such as cytokine release syndrome.

That prompted Cellectis to design "smart" CAR T cells capable of adapting to changes in the tumor microenvironment. In a proof of concept study, the company utilized synthetic biology concepts to rewire genetic circuits in three different genes of the initial T cells.

One edit made the immunotherapy more potent, but in a controlled manner to reduce off-target toxicity. The other two edits imbued CAR T cells with the ability to secrete inflammatory proteins inside the tumor microenvironment in proportion to the concentration of cancer cells.

In other words, the smart CAR T cells only asked for help from the rest of the immune system when it was needed most, which increased the anti-tumor activity of treatment and made native immune cells less likely to become neutralized. That should reduce the likelihood of triggering cytokine release syndrome, the most common (and potentially fatal) side effect of cellular medicines, which is caused by high concentrations of immune cells.

The study was conducted in mice, which means the safety and efficacy observations can't be extrapolated into humans. But that wasn't the point. The proof of concept demonstrates that the basic idea of engineering tightly controlled genetic circuits into immunotherapies is feasible. It could even allow multiple genetic circuits of the same drug candidate to be tested against one another in parallel, hastening drug development and lowering costs. Is it the inevitable future of cellular medicine?

Image source: Getty Images.

Gene editing tools are required to engineer immune cells. In fact, immunotherapies are the lowest hanging fruit for gene editing technology platforms today. It's simply easier to engineer immune cells in the lab (ex vivo) than it is to engineer specific cell types in the complex environment of the human body (in vivo).

That explains why nearly every leading gene editing company has immunotherapy programs in its pipeline. Coincidentally, all of the leading drug candidates in the industry pipeline are off-the-shelf CAR T cells engineered to treat CD19 malignancies such as non-Hodgkin's lymphoma (NHL) and B-acute lymphoblastic leukemia (B-ALL), regardless of the gene editing approach used. The smart CAR T cells designed by Cellectis targeted CD22 malignancies, but the approach could be adapted to CD19 antigen.

Developer(s)

Drug Candidate

Gene Editing Approach

Development Status

Cellectis and Servier

UCART19

TALEN

Phase 2

Precision BioSciences (NASDAQ:DTIL)

PCAR0191

ARCUS gene editing

Phase 1/2

CRISPR Therapeutics (NASDAQ:CRSP)

CTX110

CRISPR-Cas9

Phase 1/2

Sangamo Therapeutics (NASDAQ:SGMO) and Gilead Sciences (NASDAQ:GILD)

KITE-037

Zinc finger nuclease

Preclinical

Data source: Company websites.

Will these companies eventually turn to "smart" immunotherapies with regulated genetic circuits? It does seem inevitable, especially if the approach can reduce or eliminate cytokine release syndrome and enable more durable responses.

For example, Cellectis reported that all seven patients taking part in the phase 1 trial of UCART19 suffered from at least grade 1 cytokine release syndrome, which caused complications that led to the death of one patient. Five of the seven patients achieved molecular remission, but one relapsed (and remained alive) and one died. To be fair, all patients taking part in the trial had advanced, heavily pretreated B-ALL.

Precision BioSciences has encountered similar obstacles in an ongoing phase 1/2 trial of PBCAR0191. The company's lead drug candidate was administered to nine patients with NHL or B-ALL. Three cases of cytokine release syndrome were reported, but all were manageable. Seven responded to treatment, including two that achieved a complete response, but three eventually relapsed.

CRISPR Therapeutics recently began dosing patients with CTX110 in a phase 1/2 trial that will eventually enroll up to 95 individuals, but initial results won't be available until 2020. Sangamo Therapeutics and Kite Pharma, a subsidiary of Gilead Sciences, are plowing ahead with zinc fingers,but are still in preclinical development.

Investors seem pleased with most of these gene editing stocksright now. After all, despite the obstacles, current-generation cellular medicines are delivering impressive results in patient populations with relatively few options. But upcoming data readouts could easily differentiate the pack. That could increase the need to invest in augmented capabilities, such as smart immunotherapies.

There's plenty of untapped potential in cellular medicine. Today, companies are developing drug candidates with engineered CARs and TCRs designed to test hypotheses about the function of immunotherapies. As approaches find success, measured in safer and more durable responses, the next layer of complexity will be added in an effort to find even more successful therapies. And the cycle will continue.

Therefore, it seems inevitable that the field of cellular medicine will turn to smart immunotherapies with more complex genetic edits, much like the field quickly embraced the need for engineered immune cells and off-the-shelf manufacturing processes. That said, the immediate focus for Cellectis and its peers is building a stable foundation -- and those efforts have only just begun.

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Did Cellectis Just Provide a Glimpse of the Future of Cellular Medicine? - The Motley Fool

Synthetic Biology Industry Outlook to 2024 Featuring Leading Players Active Motif, Bayer, BASF, Cargill, DowDuPont, GlaxoSmithKline, Merck, Novartis…

DUBLIN--(BUSINESS WIRE)--The "Synthetic Biology: Global Markets" report has been added to ResearchAndMarkets.com's offering.

The study scope includes core synthetic biology products (e.g., oligonucleotides, synthetic genes, BioBrick parts, delivery plasmids, chassis organisms, synthetic cells, cell-based and cell-free production systems), enabling technologies (e.g., DNA sequencing, DNA synthesis, gene editing, bioinformatics, specialty media) and enabled technologies (e.g., healthcare, industrial chemicals, consumer products, food and beverage, agriculture) that are already commercialized or are forecast to be commercialized through 2024.

Key synthetic biology technologies and products are analyzed to determine present and future market status, as well as forecasted growth from 2019 to 2024. In-depth discussion of strategic alliances, industry structures, competitive dynamics, patents and market driving forces is also provided.

The author examines the synthetic biology industry by market segment, including DNA sequencing, DNA synthesis, gene editing, synthetic biology foundries and software; as well as the agriculture; consumer products, cosmetics and skin care, food and beverage, healthcare and industrial chemicals enable product sectors.

The role of key strategic alliances and acquisitions from January 2018 to September 2019 is discussed. Emerging markets, including synthetic genes, synthetic-biology-enabled drugs and vaccines, genome-edited crops and chassis organisms; as well as metabolically engineered factories for producing synthetic fuels and specialty chemicals, are analyzed, and more than 215 companies in these fields are highlighted.

The report includes:

Market Insights

The synthetic biology industry is a prime growth opportunity due to several factors. First, many of the applications for synthetic biology have large addressable markets and the penetration rate is still modest; the industry will experience explosive growth as these penetration rates accelerate. Second, development of exciting new technologies is driving innovation within the industry. These technologies include ultra-high-throughput screening platforms for organism design, enzymatic DNA synthesis and novel gene editing platforms. Third, the industry is focusing on value-added products, placing less emphasis on cost-sensitive, commodity products.

Synthetic biology foundries now routinely design, build and test designer organisms capable of producing valuable end products. The workflow includes modifying the genomes of these organisms to produce just the right combination of taste and texture, as for the food industry. Designer organisms in the textile industry help achieve the right combination of strength, flexibility, weight, dimensional variability, and targeted surface and structural modification. High-value synthetic biology end products such as these are forecast to drive significant market growth in this industry.

This report provides in-depth coverage of the dynamic synthetic biology industry, including insights into its component technologies and market segments, as well as its leading participants.

The synthetic biology industry consists of three main sets of technologies and products: enabling, core and enabled. Enabling technologies and products are the engines that drive the development of the synthetic biology industry. Core products and technologies, including standardized DNA parts, synthetic genes and chassis organisms, are the key tools by which cellular factories and systems produce enabled products.

Synthetic biology-enabled products (e.g., pharmaceuticals, chemicals, biofuels, agricultural, textiles, food) have large downstream market potential. Synthetic biology technologies add value in each of these downstream industries. In agriculture, synthetic biology makes it possible to produce crops with desired traits, such as pest resistance or high yields. Synthetic biology allows for the production of foods free of animal products, meeting an emerging consumer need in this industry.

Key Topics Covered

1. Introduction

2. Summary and Highlights

3. Overview

4. Technology Background

5. Synthetic Biology Applications

6. Synthetic Biology Industry

7. Synthetic Biology Markets

8. Patents

9. Company Profiles

For more information about this report visit https://www.researchandmarkets.com/r/9vvv4h

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Synthetic Biology Industry Outlook to 2024 Featuring Leading Players Active Motif, Bayer, BASF, Cargill, DowDuPont, GlaxoSmithKline, Merck, Novartis...

Incubator Market Growth, Analysis and Advancement Outlook – Testifyandrecap

Global Incubator Market is created to provide the market landscape and unlimited guidelines about contemporary market size, share, driving factors, trends, progressive growth, and dominant players of the Incubator Market. The report serves overall information on the market to top manufacturers, distributors, traders, dealers. It will help them understand the product scope, market overview, market driving force, technological advancement, market risk, opportunities, and research findings.

The Incubator market was valued at 950 Million US$ in 2018 and is projected to reach 1350 Million US$ by 2025, at a CAGR of 5.1% during the forecast period. In this study, 2018 has been considered as the base year and 2019 to 2025 as the forecast period to estimate the market size for Incubator.

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Key Companies Analyzed in this Report is:

Thermo Fisher Scientific, BINDER GmbH, VWR International, Sheldon Manufacturing, Panasonic, Andreas Hettich GmbH, Memmert, Weiss Technik, Heal Force Bio-meditech Holdings Limited, NuAire, JEIO TECH, Manish Scientific Instruments Company, Genlab Limited, Gemmy Industrial Corp, Shanghai Yiheng, LTE Scientific Ltd.

The leading players of Incubator industry, their market share, product portfolio, company profiles are covered in this report. The competitive market scenario among Incubator players will help the industry aspirants in planning their strategies.

Market segment by Type, the product can be split intoCarbon Dioxide IncubatorBiochemical IncubatorElectrothermal Incubator DirectlyConstant Temperature and Humidity Incubator

Market segment by Application, split intoCarbon Dioxide IncubatorBiochemical IncubatorElectrothermal Incubator DirectlyHumidity Incubator

Product Description:

In biology, an incubator is a device used to grow and maintain microbiological cultures or cell cultures. The incubator maintains optimal temperature, humidity and other conditions such as the carbon dioxide (CO2) and oxygen content of the atmosphere inside. Incubators are essential for a lot of experimental work in cell biology, microbiology and molecular biology and are used to culture both bacterial as well as eukaryotic cells.

Incubator product demand market there is also a certain space, but basically showing the scarcity of high-end products, there is a large market demand for high-end products to seize market share of imports acts.

Despite the presence of competition problems, due to the global recovery trend is clear, investors are still optimistic about this area; the future will still have more new investment enter the field.

Overview:

The growth factors of the Incubator Market are deeply discussed while the different end users of the market are underlined with the help of tables and graphs.

Further in the Incubator Market research reports, following points are included along with in-depth study of each point:-

Production Analysis Production of the Incubator is analyzed with respect to different regions, types and applications. Here, price analysis of various Incubator Market key players is also covered.

Sales and Revenue Analysis Both, sales and revenue are studied for the different regions of the Incubator Market. Also, there is a major aspect such as value, which plays an important role in the revenue generation. It is also assessed in this section for the various regions.

Supply and Consumption In continuation with sales, this section also studies the supply and consumption for the Incubator Market. This part also sheds light on the gap between supple and consumption.

Competitors In this section, various Incubator Market leading players are studied with respect to their company profile, product portfolio, capacity, price, cost and revenue.

More analysis Apart from the aforementioned information, trade and distribution analysis for the Incubator Market, contact information of major manufacturers, suppliers and key consumers is also given. Also, SWOT analysis for new projects and feasibility analysis for new investment are included.

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Major Points Covered in Table of Contents:

1 Global Incubator Market Overview

2 Global Incubator Market Competitions by Manufacturers

3 Global Incubator Capacities, Production, Revenue (Value) by Region

4 Global Incubator Supply (Production), Consumption, Export, Import by Region

5 Global Incubator Productions, Revenue (Value), Price Trend by Type

6 Global Incubator Market Analyses by Application

7 Global Incubator Manufacturers Profiles/Analysis

8 Incubator Manufacturing Cost Analysis

9 Industrial Chain, Sourcing Strategy and Downstream Buyers

10 Marketing Strategy Analyses, Distributors/Traders

11 Market Effect Factors Analysis

12 Global Incubator Market Forecast

13 Research Findings and Conclusion

14 Appendixes

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Incubator Market Growth, Analysis and Advancement Outlook - Testifyandrecap

Advances in Bispecific Antibody Development are Leading to an Evolution in Anti-cancer Drugs – OncoZine

The concept of using bispecific antibodies for tumor therapy has been developed more than 30 years ago with many initial struggles. However, new developments such as sophisticated molecular design and genetic engineering have helped tremendously in solving many technical challenges and created the next generation bispecific antibodies with high efficacy and safety profiles.

With many successes recently, the zoo of bispecific antibodies now consists of more than 100 different formats, and about 80 bispecific antibodies are currently in clinical trials.

KEYNOTE PRESENTATION: Current Landscape and Outlook of Bispecific Antibody

Roland Kontermann, PhD, Professor, Biomedical Engineering, Institute of Cell Biology and Immunology, University of Stuttgart

Bispecific antibodies have experienced a dramatic interest and growth for therapeutic applications, with more than 80 molecules in clinical development; e.g., in oncology, immuno-oncology, but also for non-oncology applications. An overview will be given on the making of bispecific antibodies and the various therapeutic concepts and applications, e.g., for dual targeting strategies, retargeting of immune effector cells, and substitution therapy by mimicking the function of natural proteins.

Functional Screening Unlocks the Therapeutic Potential of Bispecific Antibodies

Mark Throsby, PhD, CSO, Merus NV

Case studies of clinical assets will be discussed that highlight the role of empirical functional screening. Examples will include both I-O and targeted therapies demonstrating that diverse functional readouts can be incorporated into bispecific antibodies screens.

Selection-Based Development of a Heavy Chain-Light Chain Pairing Technology

Paul Widboom, PhD, Associate Director, Antibody Discovery, Adimab LLC

A significant challenge in the development of multivalent bispecific antibodies involves solving the heavy chain-light chain pairing problem. While most heavy chain-light chain pairs possess a preference for their cognate partner, noncognate mispairing occurs. Avoiding these undesired mispairs is a relevant challenge in the field of bispecific antibody manufacturing. Here we present a solution to the heavy chain-light chain problem derived from a novel selection system. This system finds mutations that improve cognate heavy chain-light chain pairing while maintaining antigen binding affinity.

A Novel Class of Fully Human Co-Stimulatory Bispecific Antibodies for Cancer Immunotherapy

Dimitris Skokos, PhD, Director, Immunity & Inflammation, Regeneron Pharmaceuticals

T-cell activation is initiated upon binding of the T-cell receptor (TCR)/CD3 complex to peptide-MHC complexes (signal 1); activation is then enhanced by engagement of a second co-stimulatory receptor, such as the CD28 receptor on T cells binding to its cognate ligand(s) on the target cell (signal 2). Recently described CD3-based bispecific antibodies act by replacing conventional signal 1, linking T cells to tumor cells by binding a tumor-specific antigen (TSA) with one arm of the bispecific, and bridging to TCR/CD3 with the other.

Next-Generation Bispecifics for Cancer Immunotherapy

Michelle Morrow, PhD, Vice President, Preclinical Translational Pharmacology, F-star

The use of bispecific antibodies can potentially modulate anti-tumour immune responses. Bispecific antibodies: an attractive alternative to cancer treatment combinations. F-stars approach to create bispecific mAb. In vitro and in vivo efficacy of F-star bispecific antibodies targeting oncology pathways observed in preclinical studies.

Bispecific Gamma Delta T Cell Engagers for Cancer Immunotherapy

Hans van der Vliet, MD, PhD, CSO, LAVA Therapeutics; Medical Oncologist, Amsterdam UMC

V9V2 T cells constitute the largest T cell subset in human peripheral blood and are powerful anti-tumor immune effector cells that can be identified in many different tumor types. This presentation will discuss bispecific antibodies designed to engage V9V2 T cells and their use for cancer immunotherapy.

Combinatorial Approaches to Enhance Bispecific Anti-Tumor Efficacy

Eric Smith, PhD, Senior Director, Bispecific Antibodies, Regeneron Pharmaceuticals

This presentation will describe Regenerons bispecific platform and present preclinical data on REGN4018, a clinical stage T cell engaging bispecific targeting Muc16 for solid tumor indications. In addition, status updates on Regenerons other clinical stage bispecific antibodies (REGN1979, REGN5458, REGN5678) will be presented as well as a discussion of new combinatorial approaches being taken to enhance bispecific anti-tumor efficacy.

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Advances in Bispecific Antibody Development are Leading to an Evolution in Anti-cancer Drugs - OncoZine