Cell Biology

GHz-Class NMR Opens New Scientific Research Window for Discoveries and Novel Insights in Functional Structural Biology and Disease Biology – Business…

BILLERICA, Mass.--(BUSINESS WIRE)--Bruker Corporation (Nasdaq: BRKR) today announced that three world-leading institutions are now accelerating their research into functional structural biology and human disease with new Bruker ultra-high field nuclear magnetic resonance (NMR) spectrometers installed in 2020. Novel GHz-class NMR technology enables advanced research to obtain structural, functional and binding information of intrinsically disordered proteins (IDPs), and of partially structured proteins with key intrinsically disordered regions (IDRs), at atomic resolution under near-physiological conditions. For example, these new technological and methods capabilities now accelerate research into viral-host interactions and viral replication, as well as into proteins that are linked to neurodegenerative diseases.

The recent installation of a 1.2 GHz NMR spectrometer at the Max Planck Institute for Biophysical Chemistry in Goettingen, has already enabled their research teams to deliver new insights into the SARS-CoV-2 nucleocapsid (N) protein, and it is set to aid the deeper molecular understanding of Parkinsons and Alzheimers diseases.

Bruker's 1.2 GHz NMR magnets utilize a novel hybrid technology with high-temperature superconductor (HTS) inserts in low-temperature superconductor outer sections. The Ascend 1.2 GHz magnets are stable, homogenous, standard-bore (54 mm) magnets suitable for high-resolution and solid-state NMR.

Using ultra-high field NMR, scientists at the Max Planck Institute (MPI) and the German Center for Neurodegenerative Diseases (DZNE) have shown that the SARS-CoV-2 N protein and host ribonucleic acids (RNA) jointly condense into tiny droplets akin to membraneless organelles, when the virus enters a host cell. This fast liquid-liquid phase separation (LLPS) inside the cytoplasm of the host cell is a characteristic capability of IDPs and IDRs, and sheds new light on how the virus replicates, and offers new targets for drug development.

Professor Christian Griesinger, Director and Scientific Member at the Max Planck Institute for Biophysical Chemistry in Goettingen, commented: The new 1.2 GHz spectrometer will allow us to characterize droplets and oligomers of IDPs that are key markers in diseases such as COVID-19, neurodegenerative diseases and cancer, and which cannot be studied using crystallography or cryo-EM.

Dr. Markus Zweckstetter, Professor at the University of Goettingen and Group Leader at the German Center for Neurodegenerative Diseases, added: Our first experiments after the installation of the new ultra-high field NMR system have focused on the SARS-CoV-2 nucleocapsid N-protein that is of key relevance for viral-host interactions and viral replication biology. The liquid-like properties of viral replication machineries in combination with the many intrinsically disordered regions of the N-protein make this research ideally suited for GHz-class NMR.

Dr. Falko Busse, President of the Bruker BioSpin Group stated: The fourth quarter acceptance at the Max Planck Institute follows installations of two 1.2 GHz NMRs at CERM (University of Florence) and at ETH Zuerich earlier in 2020. We are proud to provide enabling technology for pushing the boundaries in functional structural biology and advanced materials science.

Dr. Busse continued: We are also pleased that in December 2020, we have received an order for a second Swiss 1.2 GHz system from a consortium of the University of Zuerich, ETH Zuerich and the Biozentrum of the University of Basel. For 2021, we anticipate the installation of 4-5 GHz-class NMRs, as we have used 2020 to ramp our capacity.

About Bruker Corporation (Nasdaq: BRKR)

Bruker is enabling scientists to make breakthrough discoveries and develop new applications that improve the quality of human life. Brukers high-performance scientific instruments and high-value analytical and diagnostic solutions enable scientists to explore life and materials at molecular, cellular and microscopic levels. In close cooperation with our customers, Bruker is enabling innovation, improved productivity and customer success in life science molecular research, in applied and pharma applications, in microscopy and nanoanalysis, and in industrial applications, as well as in cell biology, preclinical imaging, clinical phenomics and proteomics research and clinical microbiology. For more information, please visit: http://www.bruker.com

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Cell Biology

IsoPlexis Announces $135 Million Financing Led by Perceptive Advisors – PRNewswire

BRANFORD, Conn., Jan. 7, 2021 /PRNewswire/--IsoPlexis, the leader in single-cell functional proteomics, today announced a $135 million Series D financing comprised of $85 million in equity securities and a $50 million credit facility. The round was led by Perceptive Advisors with participation from other new investors, Ally Bridge Group and funds and accounts managed by BlackRock, as well as other existing investors. IsoPlexis will use the proceeds from this financing to expand its global commercial and R&D teams, increase operational capacity to satisfy growing demand, and accelerate its next generation single-cell biology product development roadmap.

"We believe the future of advanced medicines will rely upon deeper access toin vivobiology for the development of new therapies and are excited to back the team at IsoPlexis," said Sam Chawla of Perceptive Advisors.

Michael Altman, of Perceptive Advisors continued, "IsoPlexis' unique technology is giving researchers this access through the convergence of dynamic proteomics and single cell biology. We are delighted to support IsoPlexis and their vision to accelerate the development of personalized therapeutics to significantly impact human health."

IsoPlexis' complete end-to-end solutions are empowered by breakthrough and proprietarysingle-cell functional proteomic technology, proteomic barcode chips, that allow researchers to phenotype each immune cell by the range of its functional proteins for the first time. Housed in its software enabled IsoLight and IsoSpark detection systems, IsoPlexis provides new and accessible layers of biological data at the single-cell level and the ability to interrogate the secreted proteome, the phosphoproteome, and the metabolome from single cells for the first time. This has allowed researchers to connect more deeply to in vivo biology and predict complex responses to therapies and disease in cancer immunotherapy, cell and gene therapy, COVID-19, autoimmune disease, and many other areas.

"We are grateful to our new and existing investors for their support of our vision," said Sean Mackay, Chief Executive Officer and Co-founder of IsoPlexis. "With more than 100 systems placed and a strong team of over 200 employees, we have laid an incredibly strong foundation for future growth at the convergence of single-cell biology, proteomics, and multi-omics. Welook forward to deploying this capital to accelerate our commercial efforts as we work to leverage our powerful biology to impact the future of advanced medicines."

About IsoPlexis

IsoPlexis is a life science technology company building solutions to accelerate the development of curative medicines and personalized therapeutics. Our award-winning single-cell proteomics systems reveal unique biological activity in small subsets of cells, allowing researchers to connect more directly to in-vivo biology and develop more precise and personalized therapies. Our integrated systems named as a top innovation or design by the Scientist Magazine, Fierce, BIG Innovation and Red Dot, among others are used globally to advance the field of single-cell biology into new 'omic possibilities as our customers generate solutions to overcome the challenges of complex diseases and therapeutics. Ourproducts have been adopted by researchers around the world, including 15 of the top 15 global pharmaceutical companies and by approximately 45% of comprehensive cancer centers. Visithttp://www.isoplexis.com to learn more.

Investor Contact:Carrie Mendivil[emailprotected]

Media Contact:Jon Chen, VP of Marketing[emailprotected]

SOURCE IsoPlexis

Single Cell Proteomics | The Superhuman Cell Company | IsoPlexis

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Cell Biology

Global Cell Biology Cloud Computing Market Revenue Analysis Report with Future Business Scope and New Investment Plans for the Next Five Years -…

The Cell Biology Cloud Computing Market study added by ResearchMoz, exhibits a comprehensive analysis of the growth trends present in the global business scenario. The study further presents conclusive data referring to the commercialization aspects, industry size and profit estimation of the market.

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Cell Biology

BlueRock Therapeutics in Collaboration with Memorial Sloan Kettering Cancer Center Receives IND Clearance for DA01 in Parkinson’s Disease – BioSpace

CAMBRIDGE, Mass., Jan. 7, 2021 /PRNewswire/ -- BlueRock Therapeutics, a preclinical stage biopharmaceutical company and wholly-owned subsidiary of BayerAG,in collaboration withMemorialSloan Kettering Cancer Center(MSK), announcedtodaythat the U.S. Food and Drug Administration (FDA) has clearedtheirInvestigational New Drug (IND) application toproceedwith aPhase 1(Ph1)study in patients with advanced Parkinson's disease (PD).This is the first trial in the United States to study pluripotent stem cell-derived dopaminergic neurons in patients with Parkinson's disease.Under the IND, BlueRockand MSK willexecute aPh1 clinical trial to evaluate the safety, tolerability andpreliminaryefficacyof DA01 in patients with PD.

"This is a big step for the stem cell field to finally test a truly "off-the-shelf" dopamine neuron product in human PD patients," said Lorenz Studer, MD, scientific co-founder of BlueRock and Director, Center for Stem Cell Biology at MSK. "We are also grateful for the visionary support by NYSTEM, the NY state-sponsored stem cell program that supported the earlier stages of this project."

"This trial is the culmination of a decade of arduous collaborative work that is based on very rigorous science. It is an important milestone on the road towards regenerative brain repair," said Viviane Tabar, MD, founding investigator of BlueRock and Chair of MSK's Department of Neurosurgery. "It is a real privilege and very exciting to be able to participate in both the bench science and the actual surgical intervention, here at MSK. Our collaborators at Weill Cornell Neurology will also be an integral part of the trial."

"Today, thereisno disease-modifying treatment for Parkinson's. Through this trial and those to follow, we hope to change that,"stated EmileNuwaysir, Ph.D., President and Chief Executive Officer of BlueRock. "Our therapy is intended to replace the midbrain dopaminergic neurons lost in the degenerative condition to rebuild the neural circuit, and thereby restore motor controlto Parkinson's patients. This could shift the treatment paradigm for millions ofPD patients, as well as demonstrate for the first time that degenerative disease is, in principle, reversible. We believe this would represent an enormous step forthe PD community worldwide, and formedicine."

The trial plans to enroll ten patients starting with a first clinical site at Weill Cornell Medicinein the initial open-label study. The primary objective of thePh1study is to assess the safety and tolerability of DA01 cell transplantation at one-year post-transplant. The secondary objectives of the study are to assess the evidence of transplanted cell survival and motor effects at one- and two-years post-transplant, to evaluate continued safety and tolerability at two years, and to assess feasibility of transplantation.

About Parkinson's DiseaseParkinson's disease is a progressive neurodegenerative disorder caused by nerve cell damage in the brain, leading to decreased dopamine levels. The worsening of motor and non-motor symptoms is caused by the loss of dopamine-producing neurons. At diagnosis, it is estimated that patients have already lost 60-80% of their dopaminergic neurons.Parkinson's disease often starts with a tremor in one hand. Other symptoms are rigidity, cramping and dyskinesias. Parkinson's disease is the second most common neurodegenerative disorder, impacting more than 7.5 million people, including 1.3 million people in North America.

About BlueRock TherapeuticsBlueRock Therapeutics is a leading engineered cell therapy company with a mission to develop regenerative medicines for intractable diseases. BlueRock Therapeutics' cell+gene platform harnesses the power of cells to create new medicines for neurology, cardiology and immunology indications. BlueRock Therapeutics' cell differentiation technology recapitulates the cell's developmental biology to produce authentic cell therapies, which are further engineered for additional function. Utilizing these cell therapies to replace damaged or degenerated tissue brings the potential to restore or regenerate lost function. BlueRock Therapeutics was founded in 2016 by Versant Ventures and Bayer AG and capitalized with one of the largest-ever Series A financings in biotech history by Bayer AG (through its Leaps by Bayer unit) and Versant Ventures. The company was fully acquired by Bayer in 2019. BlueRock Therapeutics' culture is defined by scientific innovation, the highest ethical standards and an urgency to bring transformative treatments to all who would benefit. For more information, visit bluerocktx.com.

About BayerBayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2019, the Group employed around 104,000 people and had sales of 43.5 billion euros. Capital expenditures amounted to 2.9 billion euros, R&D expenses to 5.3 billion euros. For more information, visit bayer.com.

DisclosuresDr. Studer has intellectual property rights and interests and financial interests related to BlueRock. Dr. Tabar has financial interests related to BlueRock. Researchers at Memorial Sloan Kettering Cancer Center, including Dr. Studer, developed stem cell-derived dopaminergic neurons for the treatment of neurodegenerative diseases, and MSK licensed this intellectual property to BlueRock. MSK has institutional financial interests related to this intellectual property and BlueRock.

Forward-Looking StatementsCertain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as "anticipate," "believe," "forecast," "estimate" and "intend," among others. These forward-looking statements are based on BlueRock's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, the timing of our clinical trial for DA01; our results regarding the safety, tolerance and efficacy of DA01 cell transplantation for patients with Parkinson's disease; and ongoing FDA and other regulatory requirements regarding the development of DA01. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Except as expressly required by law, BlueRock does not undertake an obligation to update or revise any forward-looking statement. All of the Company's forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date hereof.

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BlueRock Therapeutics in Collaboration with Memorial Sloan Kettering Cancer Center Receives IND Clearance for DA01 in Parkinson's Disease - BioSpace

Cell Biology

Study monitors spatial shifts of liver gene expression in relationship to the circadian clock – News-Medical.net

Nothing in biology is static. Biological processes fluctuate over time, and if we are to put together an accurate picture of cells, tissues, organs etc., we have to take into account their temporal patterns. In fact, this effort has given rise to an entire field of study known as "chronobiology".

The liver is a prime example. Everything we eat or drink is eventually processed there to separate nutrients from waste and regulate the body's metabolic balance. In fact, the liver as a whole is extensively time-regulated, and this pattern is orchestrated by the so-called circadian clock, our body's internal metronome, as well as biochemical signals and eating rhythms.

But the liver is actually divided into small repeating units called "lobules", in which distinct zones perform different functions. This intricate spatial organization is known as "liver zonation". For example, the breakdown of sugars during digestion takes place preferentially on one side of the lobule, the so-called central zone, while the production of glucose while we rest from stores such as fat, occurs on the other side of the liver, at the portal side.

So far, liver zonation has only been studied statically, looking into what each zone does independently of time, and vice-versa. And given how central the liver is in mammalian physiology, the two research approaches have to join efforts to understand how temporal and spatial liver programs interact.

In a first ever study, scientists at EPFL and the Weizmann Institute of Science, led by Professors Felix Naef at EPFL's School of Life Sciences and Shalev Itzkovitz at the Weizmann, have been able to monitor the spatial shifts of gene expression within liver lobules in relationship to the circadian clock. Studying this link is a focus of Naef's research, which has previously uncovered connections between the circadian clock and the liver's proteins, our cell cycles, and even the 3D structure of chromatin, the tightly packaged DNA in the cell nucleus.

The study came out of a EPFL-Weizmann joint grant from the Rothschild Caesarea Foundation.

By exploiting the ability to analyze liver tissue in every individual cell, the researchers studied approximately 5000 genes in liver cells at several timepoints throughout the 24-hour day. They then statistically classified the space-time patterns they uncovered with a model that can capture both spatial and temporal variations in the levels of messenger RNA (mRNA), a marker of gene expression.

The study revealed that many of the liver's genes seem to be both zonated and rhythmic, meaning that they are regulated by both their location in the liver and the time of the day. These dually regulated genes are mostly linked to key functions of the liver, e.g. the metabolism of lipids, carbohydrates, and amino acids, but also include a few genes that have never been associated with metabolism, e.g. genes related to chaperone proteins, which help other biomolecules change their 3D structure or even assemble and disassemble.

The work reveals a richness of space-time gene expression dynamics of the liver, and shows how compartmentalization of liver function in both space and time is hallmark of metabolic activity in the mammalian liver."

Felix Naef, EPFL's School of Life Sciences

Source:

Journal reference:

Droin, C., et al. (2021) Space-time logic of liver gene expression at sub-lobular scale. Nature Metabolism. doi.org/10.1038/s42255-020-00323-1.

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Cell Biology

Researchers determine the atomic structure of protein that helps coronavirus to evade immune cells – News-Medical.net

A team of HIV researchers, cellular biologists, and biophysicists who banded together to support COVID-19 science determined the atomic structure of a coronavirus protein thought to help the pathogen evade and dampen response from human immune cells.

The structural map - which is now published in the journal PNAS, but has been open-access for the scientific community since August - has laid the groundwork for new antiviral treatments tailored specifically to SARS-CoV-2, and enabled further investigations into how the newly emerged virus ravages the human body.

Using X-ray crystallography, we built an atomic model of ORF8, and it highlighted two unique regions: one that is only present in SARS-CoV-2 and its immediate bat ancestor, and one that is absent from any other coronavirus. These regions stabilize the protein - which is a secreted protein, not bound to the membrane like the virus's characteristic spike proteins - and create new intermolecular interfaces. We, and others in the research community, believe these interfaces are involved in reactions that somehow make SARS-CoV-2 more pathogenic than the strains it evolved from."

James Hurley, Lead Author, Professor, UC Berkeley, Former Faculty Scientist, Lawrence Berkeley National Laboratory (Berkeley Lab)

Generating protein structure maps is always labor intensive, as scientists have to engineer bacteria that can pump out large quantities of the molecule, manipulate the molecules into a pure crystalline form, and then take many, many X-ray diffraction images of the crystals. These images - produced as X-ray beams bounce off atoms in the crystals and pass through gaps in the lattice, generating a pattern of spots - are combined and analyzed via special software to determine the location of every individual atom. This painstaking process can take years, depending on the complexity of the protein.

For many proteins, the process of building a map is helped along by comparing the unsolved molecule's structure to other proteins with similar amino acid sequences that have already been mapped, allowing scientists to make informed guesses about how the protein folds into its 3D shape.

But for ORF8, the team had to start from scratch. ORF8's amino acid sequence is so unlike any other protein that scientists had no reference for its overall shape, and it is the 3D shape of a protein that determines its function.

Hurley and his UC Berkeley colleagues, experienced in structural analysis of HIV proteins, worked with Marc Allaire, a biophysicist and crystallography expert at the Berkeley Center for Structural Biology, located at Berkeley Lab's Advanced Light Source (ALS). Together, the team worked in overdrive for six months - Hurley's lab generated crystal samples and passed them to Allaire, who would use the ALS's X-ray beamlines to take the diffraction images. It took hundreds of crystals with multiple versions of the protein and thousands of diffraction images analyzed by special computer algorithms to puzzle together ORF8's structure.

"Coronaviruses mutate differently than viruses like influenza or HIV, which quickly accumulate many little changes through a process called hypermutation. In coronaviruses, big chunks of nucleic acids sometimes move around through recombination," explained Hurley. When this happens, big, new regions of proteins can appear.

Genetic analyses conducted very early in the SARS-CoV-2 pandemic revealed that this new strain had evolved from a coronavirus that infects bats, and that a significant recombination mutation had occurred in the area of the genome that codes for a protein, called ORF7, found in many coronaviruses. The new form of ORF7, named ORF8, quickly gained the attention of virologists and epidemiologists because significant genetic divergence events like the one seen for ORF8 are often the cause of a new strain's virulence.

"Basically, this mutation caused the protein to double in size, and the stuff that doubled was not related to any known fold," added Hurley. "There's a core of about half of it that's related to a known fold type in a solved structure from earlier coronaviruses, but the other half was completely new."

Like so many scientists working on COVID-19 research, Hurley and his colleagues opted to share their findings before the data could be published in a peer-reviewed journal, allowing others to begin impactful follow-up studies months earlier than the traditional publication process would have allowed. As Allaire explained, the all-hands-on-deck crisis caused by the pandemic shifted everyone in the research community into a pragmatic mindset. Rather than worrying about who accomplished something first, or sticking to the confines of their specific areas of study, scientists shared data early and often, and took on new projects when they had the resources and expertise needed.

In this case, Hurley's UC Berkeley co-authors had the viral protein and crystallography expertise, and Allaire, a longtime collaborator, was right up the hill, also with crystallography expertise and, critically, a beamline that was still operational. The ALS had received special funding from the CARES Act to remain operational for COVID-19 investigations. The team knew from reviewing the SARS-CoV-2 genomic analysis posted in January that ORF8 was an important piece of the (then much hazier) pandemic puzzle, so they set to work.

The authors have since all moved on to other projects, satisfied that they laid the groundwork for other groups to study ORF8 in more detail. (Currently, there are several investigations underway focused on how ORF8 interacts with cell receptors and how it interacts with antibodies, as infected individuals appear to produce antibodies that bind to ORF8 in addition to antibodies specific to the virus's surface proteins.)

"When we started this, other projects had been put on hold, and we had this unique opportunity to hunker down and solve an urgent problem," said Allaire, who is part of Berkeley Lab's Molecular Biophysics and Integrated Bioimaging Division. "We worked very closely, with a lot of back and forth, until we got it right. It really has been one of the best collaborations of my career."

Source:

Journal reference:

Flower, T.G., et al. (2021) Structure of SARS-CoV-2 ORF8, a rapidly evolving immune evasion protein. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2021785118.

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Cell Biology

Researchers investigate protein phosphatase to identify new treatments for cancer, other diseases – News-Medical.Net

The abundant presence of an enzyme known as low molecular weight protein tyrosine phosphatase (LMWPTP) in tumor cells has long been considered an indicator of cancer aggressiveness and metastatic potential. It is also known to perform important functions in cells under normal conditions, participating in both the proliferation process and the regulation of intracellular systems. Research continues on its role in cancer progression.

In Brazil, a group of researchers at the University of Campinas's In Vitro Bioassay and Signal Transduction Laboratory led by Professor Carmen Verssima Ferreira-Halder are studying the possibility of inhibiting this protein phosphatase to create novel opportunities for monitoring and treatment of cancer and other diseases.

We believe inhibition of LMWPTP could contribute to the treatment of several diseases. In our case, the focus is on cancer, but research shows it's also associated with autoimmune diseases and diabetes, among others."

Carmen Verssima Ferreira-Halder, Professor, In Vitro Bioassay and Signal Transduction Laboratory, University of Campinas

Ferreira-Halder was principal investigator for the Thematic Project "Low molecular weight protein tyrosine phosphatase in colorectal cancer: from the bench to product generation", supported by FAPESP and completed in June 2020.The phosphatase favors the action of intratumor proteins that help tumors divide, migrate and establish metastasis. "For this reason we say it's a 'hub', in the sense that it controls several processes which together make tumor cells resistant to treatment and able to migrate and establish metastasis," she said.

A review article by the group published in Cellular and Molecular Life Sciences outlines 14 years of research on LMWPTP and its contribution to cancer treatment. "Our group was one of the first to show that this enzyme contributes to chemotherapy resistance in leukemia cells," Ferreira-Halder said. "We also found that the more advanced the stage of the tumor, the larger the amount of the enzyme.

With these discoveries as a basis, research conducted in collaboration with the group led by Professor Maikel Peppelenbosch at Erasmus University Medical Center in Rotterdam [Erasmus MC, Netherlands] validated the significance of LMWPTP to other types of cancer, such as prostate, colorectal and stomach cancer. This research showed us that LMWPTP not only weakens the response to chemotherapy drugs but is also associated with a greater capacity for metastasis."

The review article, whose first author is Alessandra Valria de Sousa Faria, also discusses the available substances that inhibit LMWPTP and the characteristics that make it difficult for drugs to be designed against it. Ferreira-Halder believes it is not yet possible to speak of treatment based on inhibition of LMWPTP, but the strategy can be used for other purposes.

"Our initial aim is to use this enzyme as a biomarker for the purpose of monitoring treatment, and also to use it to classify patients in terms of the severity of disease. In my view this can be done in a relatively short time," she said. "As for treatment, a lot more work remains to be done. Professor Nunzio Bottini at the University of California San Diego [USA] has filed for a patent on a highly effective inhibitor that can be administered orally. Actually he and his group have synthesized several inhibitors, but they have only published one. Maybe we're in for a surprise and a drug will be developed faster. Who knows?"

The main challenges to be faced in developing inhibitors are specificity the drug must act specifically on LMWPTP, which is part of a family of some 100 highly similar phosphatases and stability, so that the drug remains active in the organism. "Until Bottini and his group filed their patent application, all inhibitors acted on several members of the family," Ferreira-Halder said.

Some of the substances mentioned in the review were developed for other purposes but also inhibit LMWPTP and could be used to treat cancer, according to Faria, who recently defended her doctoral thesis on how LMWPTP affects platelets, small cell fragments in the bloodstream that play a key role in clotting.

Faria's research on LMWPTP began with its role in colorectal cancer and platelet reaction in this microenvironment. "As our investigation of platelet biology progressed, we realized how much more knowledge of the enzyme's action on platelets was needed," she said.

The first part of the study consisted of verifying the action of LMWPTP and the protein tyrosine phosphatase 1B (PTP1B) on platelets, with regard to both metabolism and function. The second focused on the influence of platelets on the expression of LMWPTP in cells.

"The goal was to find out to what extent tumor cells may 'educate' platelets to support certain events, such as metastasis, for example, and conversely how far platelets 'educate' tumor cells to assure their survival and proliferation," Faria explained.

For Ferreira-Halder, the relationship appears to be two-way. "However, the action of tumor cells probably predominates. They practically program platelets to work in their favor," she said.

Ferreira-Halder and her group have collaborated with Peppelenbosch's since 2004, but work on the Thematic Project completed in June began only 2016, she recalled, adding that experiments conducted by Emanuella Maria Barreto Fonseca and Cludia de Lourdes Soraggi at Peppelenbosch's laboratory provided a vitally important foundation for the initial hypotheses. Fonseca was supported by a postdoctoral fellowship from FAPESP. Soraggi was able to attend an overseas training course thanks to support from the University of Campinas (UNICAMP) via its Executive Vice Rectorship for International Relations.

"In our Thematic Project research, we were able to investigate the action of this phosphatase from various angles and validate the hypothesis of its role in other tumors besides chronic myeloid leukemia," Ferreira-Halder said. "We wanted to uncover the mechanism of its action, and we now have a great deal of information about this action not just inside but also outside the tumor, because we set out to see if LMWPTP also influenced the tumor's microenvironment external to the cancer cells."

Other research interests for the group during the project included: extracellular vesicles (nanometer-sized structures that play an important role in intercellular communication), with Stefano Piatto Clerici supported by FAPESP showing that LMWPTP regulates these vesicles; platelets, studied by Faria, also with a scholarship from FAPESP; and the TGF-beta signaling pathway, which is involved in many cellular processes such as proliferation and differentiation and was studied by Helon Guimares Cordeiro.

The network of collaborators continued to expand, adding an expert in platelet biology (Sheila Siqueira Andrade at PlateInnove Biotech), and a hematologist and an oncologist at Erasmus MC (Moniek de Maat and Gwenny Fuhler respectively).

According to Ferreira-Halder, the Thematic Project has so far spawned 15 publications (eight articles and two book chapters, as well as five articles under peer review), and several other research fronts. A new project in the same line of research is currently being designed.

Source:

Journal reference:

Faria, A.V. S., et al. (2020) Low molecular weight protein tyrosine phosphatase as signaling hub of cancer hallmarks. Cellular and Molecular Life Sciences. doi.org/10.1007/s00018-020-03657-x.

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Cell Biology

Aviceda Therapeutics Announces Formation of Executive Team – Business Wire

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Aviceda Therapeutics, a late-stage, pre-clinical biotech company focused on developing the next generation of immuno-modulators by harnessing the power of glycobiology to manipulate the innate immune system and chronic, non-resolving inflammation, is announcing the composition of the Executive Team that will guide the company through ongoing development of breakthrough, first-in-class therapeutics and continued growth opportunities as a business entity.

Serving in key leadership roles on Avicedas Executive Leadership Team will be:

Aviceda is extremely proud of the world-class team of internationally renowned experts we have assembled to guide the company in the next phases of growth. In addition to offering keen scientific insight into product development, each member of the Executive Team also brings with them previous experience in key leadership positions in the pharmaceutical industry. Being able to tap into this knowledge base will undoubtedly pay huge dividends as Aviceda pursues an aggressive but realistic growth and product development strategy, said Dr. Genead, who is a Co-Founder of Aviceda.

A serial life-sciences entrepreneur, senior innovative biopharma executive, inventor, and consultant to many ophthalmic biotechnology companies and healthcare venture firms, Dr. Genead is widely regarded as a global executive and senior leader with 20-plus years experience in pharmaceutical drug and business development with execution from discovery to late development and commercial phases. He has played key roles in executing global approvals and launches and driving sales growth in country, regional and global development positions together with direct reporting teams.

Dr. Genead previously served as Chief Medical Officer and Executive Vice-President for GenSight Biologics where he led the clinical team to multiple phase I-III trials leveraging a disruptive ocular gene therapy and optogenetics platforms in patients with retinal degenerative diseases. Prior to GenSight, Dr. Genead was Biogens Head of Ophthalmology and Retina Gene Therapy. Dr. Genead has also held leadership positions with Allegro Ophthalmics, where he led the global clinical development teams for the Risuteganib (anti-integrin) platform, and Allergan, where he was Global Medical Director and Clinical Team Lead for Retina Therapeutic area. Dr. Genead is a Co-founder of several start-ups, has been instrumental in the raising of over $500M in venture and institutional capital for numerous life sciences biotech companies and is currently a board member of several ophthalmic organizations and scientific advisory boards. Dr. Genead is a board-certified ophthalmologist/retina specialist by training, having completed a vitreoretinal fellowship at the Department of Ophthalmology and Visual Sciences of the University of Illinois in Chicago and Medical College of Wisconsin. He has served as a principal Investigator with a proven record of success in developing and launching global blockbuster therapeutics. He was the primary and key author for numerous peer-reviewed manuscripts in high impact factor scientific journals (more than 100 manuscripts and presentations) focusing on clinical research and novel therapeutics.

Dr. Callanan is a board-certified ophthalmologist, a clinical Professor at the University of Texas Southwestern Medical School in Dallas, Texas and surgeon with Texas Retina Associates, specializing in vitreoretinal diseases including uveitis, diabetic retinopathy and age-related macular degeneration.

Dr. Callanan earned his medical degree at the University of Iowa College of Medicine and completed his ophthalmology residency at Parkland Memorial Hospital, University of Texas Southwestern Medical Center. He received a National Research Service Award from the National Institutes of Health for the study of Ocular Immunology with Dr. Jerry Niederkorn. He was a Heed Ophthalmic Foundation Fellow at the prestigious Bascom Palmer Eye Institute in Miami, Florida. He completed fellowships in medical retina with legendary Dr. J. Donald M. Gass and vitreoretinal surgery with the Bascom Palmer faculty. Dr. Callanan also received additional training in uveitis with Dr. Robert Nussenblatt at the National Eye Institute in Bethesda, over 60 peer reviewed articles and several book chapters, Dr. Callanan is widely regarded as a respected leader in his field. Throughout his career he has actively conducted clinical research and has played an instrumental role in several ophthalmic drug approvals. In addition to his clinical and academic responsibilities, Dr. Callanan also serves on the board of directors of the Retina Foundation of the Southwest and is a member of numerous professional and honorary societies, including the American Academy of Ophthalmology, The Association for Research in Vision and Ophthalmology, The Macula Society, The American Uveitis Society, and the American Society of Retina Specialists, among others.

I am thrilled to join Aviceda at an exciting time for the company and its portfolio of pipeline candidates. Glyco-immune therapeutics offers the prospect of a truly transformational approach to treating a variety of underserved immune mediated inflammatory conditions that do not have adequate therapeutic options. While our immediate focus will be on ophthalmic conditions, there is tremendous potential to improve treatment options for a wide assortment of conditions affecting the innate immune system, said Dr. Callanan.

Dr. Kunimoto, who is a co-Founder of Aviceda, holds a medical degree with honors from Harvard Medical School and a law degree with honors from Oxford University, which he attended on a Rhodes Scholarship. He was a medicine intern at Massachusetts General Hospital and completed his residency at Wills Eye Hospital in Philadelphia, where he served as co-chief resident. Dr. Kunimoto was recognized as a Heed and Michaels Fellow. He worked as a consultant with the management consultancy, McKinsey & Co. Dr. Kunimoto has authored numerous peer-reviewed publications, two major ophthalmology textbooks, and has been invited to speak at ophthalmology conferences, both nationally and internationally. Dr. Kunimoto has been very active in the clinical research of retinal diseases, acting as Investigator or Principal Investigator in over 150 global clinical trials. A recipient of numerous honors for academic and research achievements, Dr. Kunimoto served as Managing Partner of Retinal Consultants of Arizona, where he lead efforts to grow the practice to 35 locations, develop a nutraceutical franchise, and establish an Aviation Department for transportation and patient coverage at outlying satellite offices. He also served as Manager of the Retina Research Institute. Dr. Kunimoto is a founding member and served as Founding President of the Vit-Buckle Society, served as Chair of the Medical Student Governing Council in the Massachusetts Medical Society, and as a member on the Council on Constitution and Bylaws of the American Medical Association. Outside of medicine, Dr. Kunimoto serves on the Board of Directors of the Association of American Rhodes Scholars.

Prior to graduating with a medical degree from the University of Massachusetts, Dr. Tolentino performed research on retinal degeneration at the Schepens Eye Research Institute and the Berman Gund Lab (both at Harvard Medical School), as well as the National Eye Institute. After Medical School, Dr. Tolentino did a post-doctoral angiogenesis research fellowship in the lab of Dr. Judah Folkman, where he helped develop a cancer/xenograft model to screen for angiogenic inhibitors, work that demonstrated the role of Vascular Endothelial Growth Factor (VEGF) in macular degeneration, diabetic retinopathy and vein occlusion. During this time he purified Bevacizumab (Avastin), a drug designed for oncologic applications, and demonstrated intravitreal application could inhibit ocular neovascularization, a discovery that led to the eventual development of anti-VEGF therapeutics for retinal disease. After finishing his Ophthalmology Residency, Dr. Tolentino joined the retina and molecular ophthalmology faculty at the University of Pennsylvania, where he ran a lab funded by the National Institutes of Health working on gene, cell and RNAi therapy. Among his many accomplishments is the invention of a new class of gene silencing molecules called small interfering RNA (siRNA) against anti-angiogenic targets. He has 3 issued patents on the composition and methods of use of these molecules in vertebrate organisms for treating neovascular diseases. The discovery of siRNA and its mechanisms in invertebrate worms resulted in the Nobel prize in Medicine for Craig Mello and Andrew Fire in 2006. Dr. Tolentino co-founded and served as the interim CEO/CSO for Acuity Pharmaceuticals, where he was able to herald the first siRNA therapeutic into human clinical trials. Acuity eventually merged with Exegenic Inc to form OPKO health (NYSE: OPK), a publicly traded biopharmaceutical company. Over the course of his career, Dr. Tolentino has been very active in the clinical research of retinal diseases, acting as principal investigator in over 150 clinical trials that led to multiple global approvals for retinal therapeutics. He has authored over 100 publications and delivered over 200 international lectures. He has served as a consultant/scientific advisor for numerous pharma/biotech companies.

Prof. Scott, Aviceda Scientific Co-Founder, is Director of the Patrick G Johnston Centre for Cancer Research and Cell Biology at Queens University Belfast. He is internationally renowned for his work in development of novel approaches in the field of antibody and nanomedicine-based therapies for the treatment of cancer and other conditions. Prof. Scott has a background in both the pharmaceutical industry and academia and was a founding scientist of Fusion Antibodies Plc. Research in his laboratory is funded by agencies such as Medical Research Council, UK charities and various industrial sources. He also held a Royal Society Industrial Fellowship with GSK from 2012 to 2015 and won the Vice Chancellors Prize for Innovation in 2015 with his groups work on developing a novel Siglec targeting nanomedicine for the treatment of sepsis and other inflammatory conditions.

About Aviceda Therapeutics

Founded in 2018 and based in Cambridge, Massachusetts, Aviceda Therapeutics is a late-stage, pre-clinical biotechnology company with a mission to develop the next generation of glyco-immune therapeutics (GITs) utilizing a proprietary technology platform to modulate the innate immune system and chronic, non-resolving inflammation. Aviceda has assembled a world-class, cross-disciplinary team of recognized scientists, clinicians and drug developers to tackle devastating ocular and systemic degenerative, fibrotic, oncologic and immuno-inflammatory diseases. At Aviceda, we exploit a unique family of receptors expressed on all innate immune cells and their associated glycobiological interactions to develop transformative medicines. Combining the power of our biology with our innovative cell-based high-throughput screening platform and proprietary nanoparticle technology, we can modulate the innate immune response specifically and profoundly. Aviceda is developing a pipeline of GITs that are delivered via biodegradable nanoparticles and which safely and effectively target numerous immune-inflammatory conditions. Avicedas lead ophthalmic optimized nanoparticle, as an intravitreal formulation, AVD-104, is being developed to target various immune system responses that contribute to the pathology associated with age-related macular degeneration (AMD).

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Aviceda Therapeutics Announces Formation of Executive Team - Business Wire

Embryology

TMRW Adds Three High Profile Hires To Its Senior Executive Team – PRNewswire

NEW YORK, Jan. 12, 2021 /PRNewswire/ -- TMRW Life Sciences("TMRW"), creator ofthe first and only automated technology platform for the management, identification, and storage of frozen eggs and embryos, announced todaythe recent hiring of Todd Ballard as Chief Marketing Officer; Rohit Gupta as SVP & Chief Biobank Officer; and, Gene Shkolnikov as SVP, Product.

With this exceptional trio, TMRW continues to strengthen its executive team as it prepares to announce acceleration into commercial operations.

Todd Ballardcomes to TMRW after a highly successful, 12 year tenure at GoPro. As Chief Marketing Officer, he directed the global marketing, brand development, and media vision for the $1B+ cutting-edge technology company. He joined GoPro when it was an early stage start-up, was instrumental in the company's IPO, and led its celebrated marketing involving annual budgets of more than $100 million and a dedicated team of over 140 people. Under Todd's leadership, GoPro invented an entirely new consumer category, elevating a camera company into a well-known lifestyle brand. Understanding the importance of fostering strong connections, he built relationships with hundreds of global celebrities, artists, producers/directors, and athletes. He also cut large business development and licensing deals with major broadcast networks and sports leagues, including NBC, Sports Illustrated, the NHL, MotoGP, Tour de France, PGA, and X Games, among others.

With a wide range of both B2B and B2C marketing experience, Todd's 25 years of expertise and entrepreneurial spirit will be pivotal to TMRW's success. As TMRW's CMO, Todd will develop and champion the marketing strategy, leading all aspects of product marketing and digital marketing, social media, as well as branding and PR.

Rohit Guptahas over 15 years of experience at the forefront of biobanking, data science, and research, earning him a well-deserved reputation as one of the elite biobanking experts in the world. He has a proven history of leadership in both cryo-management operations, innovation and research. Among his many accomplishments, Rohit was the Chief Biobank Officer at the University of California, San Francisco (UCSF) where he led that institution's landmark work to support cutting edge precision medicine research. His next generation approach to biobanking aimed at not only absolutely assuring the highest standards of care for specimens, but also at enabling cutting edge biomedical research. Earlier in his career, Rohit was the Executive Director, Stanford Biobank & Clinical Research Services at Stanford University,where he played a key role in supporting Stanford's entire medical research effort. His work was pivotal in securing over $100M in research grants at Stanford and UCSF. In addition to his biobanking roles, Rohit also recently served as Conference Co-Chairman of the International Society for Biological and Environmental Repositories (ISBER), the global leading authority establishing standards, education, ethical principles, and innovation in the science and management of biorepositories. He has co-authored several industry publications and is the recipient of numerous honors, grants, and awards, and is a sought-after speaker and lecturer at global industry events.

As TMRW's SVP & Chief Biobank Officer, Rohit will focus on building on TMRW's commitment to the highest levels of operational excellence, particularly as it relates to the cryo-management aspects of caring for the human eggs and embryos in the TMRW platform. In addition, he will be deeply involved in TMRW's continued innovation including product/technology, data collection, privacy, and integration efforts, government and regulatory affairs activities and peer reviewed research studies.

Gene Shkolnikovjoins TMRW from Johnson & Johnson, where he built and led a large, global engineering team responsible for building and launching innovative Internet of Things ("IoT") platforms as part of a global digital business transformation. His work led to multiple new product lines spanning the Pharma R&D, medical device, and manufacturing sectors. Additionally, Gene collaborated across the organization on big data strategy, including analytics, artificial intelligence, and machine learning. He holds several patents, having created breakthrough products in the mobile, IoT, healthcare, and wearable technology sectors. Highly skilled in operating at the forefront of emerging technologies and transforming them into innovative products and solutions, over the course of his career at both J&J and as an independent entrepreneur, Gene has built teams from the ground up, raised capital, become an industry leader, and launched award-winning products resulting in licensing deals with Fortune 500 clients.

As TMRW's SVP of Product, Gene will lead the development of all TMRW hardware, labware, and sensors.

"The simultaneous appointment of these three key executives, all proven leaders in their respective fields, speaks to TMRW's commitment to bringing together world class talent from diverse fields to make the management and storage of the frozen eggs and embryos that will be used in hundreds of millions of IVF procedures truly safe, secure, and reliable," says Joshua Abram, Founder and co-CEO of TMRW.

In the past year, TMRW has doubled its headcount. Launching commercially in late January, the company is poised to continue its exponential growth in the coming months. By the end of 2021, TMRW will be used in clinics accounting for more than 30% of all IVF cycles in the U.S. The company anticipates launching internationally in summer 2021.

About TMRW Life Sciences, Inc.TMRW has created the world's first automated platform designed specifically for cryo-management of eggs and embryos used in IVF. TMRW's RFID-enabled, complete digital chain of custody SaaS technology radically improves upon the error-prone manual and analog methods that have gone unchanged throughout the history of IVF, significantly reducing the chances of implantation mix-ups or loss of eggs and embryos. The TMRW team includes many of the world's most celebrated innovators in fertility, embryology, cryo-management, automation, software development and robotics to name a few of the disciplines involved. TMRW's co-founders, Joshua Abram, Alan Murray, and Dr. Jeffrey Port, are serial tech and life sciences entrepreneurs. Their immediate prior ventures sold for a combined sum of more than $1 billion. To date, TMRW has raised $50 million. For more information, please visit TMRW.org.

Media ContactEmily Grosser, Dini von Mueffling Communications[emailprotected] 757-645-5190

SOURCE TMRW Life Sciences

http://www.tmrw.org

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TMRW Adds Three High Profile Hires To Its Senior Executive Team - PRNewswire

Anatomy

Anatomy of a wild-card win: The three-pronged plan that has Tampa Bays offense humming – Yahoo Sports

When the Buccaneers face the Washington Football Team in the wild-card round on Saturday night, the obvious issue for the Bucs offense is a Washington defensive line stacked with five first-round picks (Chase Young, Montez Sweat, Jonathan Allen, Daron Payne, and Ryan Kerrigan) and the interior pressure that front five can create.

Interior pressure has always been Bradys Kryptonite (as one half-smart football scholar pointed out this week), and Brady has not been great at all under pressure this season per Pro Football Focus, hes faced pressure on 155 of his 636 dropbacks, and hes completed 57 of 130 attempts for 675 yards, four touchdowns, five interceptions, and a passer rating of 54.5 the ninth-worst passer rating under pressure among quarterbacks who have taken at least 50% of their teams snaps.

But if Tampa Bays offensive line is able to mitigate that furious pass rush and with guards Alex Cappa and Ali Marpet and center Ryan Jensen, they very well could Washington could be in big trouble in a big hurry.

The relationship between Brady and Bucs head coach Bruce Arians and offensive coordinator Byron Leftwich has taken a while to solidify, but its happened in the last month, for multiple reasons. After a first half of the season in which Brady and his receivers were rarely on the same page, leading to some embarrassing helium throws, everyones adhered themselves to the same playbook. Brady and his targets are in sync, and Arians and Leftwich have this offense humming with three things play-action, pre-snaop motion, and 12 personnel two tight ends, two receivers, and one running back.

Story continues

Brady had just 67 play-action snaps from Weeks 1-9 the third-fewest in the league behind Philip Rivers and Kirk Cousins and he threw six touchdown passes to two interceptions. Without play-action, he threw 14 touchdowns and five picks. In Weeks 10-17, Brady dropped back on 58 snaps with play-action in Weeks 10-17 with seven touchdowns and one interception to show for it. Without play-action in the second half of the season, Brady threw 13 touchdown passes to four picks. So, maybe its time to dial that up a bit more.

Arians has been resistant to pre-snap motion this season, saying at one point that Peyton Manning didnt need it when Arians was coaching Manning with the Colts from 1998 through 2000, but its a different league now, and Brady benefited greatly from motion during his time with the Patriots. Brady has utilized pre-snap motion for years to help discern coverage concepts, to isolate and remove specific defenders, and to give his receivers an advantage that their physical gifts dont always present.

But its been a bigger part of Tampa Bays offense lately, and the results are obvious in a positive sense. From ESPNs Seth Walder:

This touchdown from Brady to Chris Godwin last Sunday is a perfect example of how motioning a receiver across the formation not only gives Brady a zone indicator, but also creates an unfavorable matchup for the Falcons defense. Safety Keanu Neal checks linebacker Foyesade Oluokun to trail Godwin on the slot fade, and thats not the best call.

Add in the specter of 12 personnel, which is the personnel on this play, and another advantage becomes clear with two tight ends in the formation, there are more blockers. This is especially true when one of those tight ends is Rob Gronkowski, the best blocking tight end of his era. Its one reason Brady has been more willing to take deep shots out of 12.

With 12 personnel and play-action since Week 13, Brady completed 12 of 20 passes for 239 yards, 108 air yards, five touchdowns, one interception. On attempts of 20 or more air yards in those same circumstances, Brady had five attempts, four completions, two touchdowns, one interception. If you see the Bucs in 12, the deep shot is coming.

Heres another example against the Lions hapless pass defense in Week 16. The Bucs have Gronk and Cameron Brate aligned to the right side. Subtle pre-snap motion moving Brate inside tells Brady that Detroit is playing man coverage (which Detroit should never do), the stack creates coverage confusion off the snap, and then its yet another Brady-to-Gronk deep fade in which Gronk bodies the poor defender for the 33-yard touchdown.

Its almost like those two guys have been there before.

Washington doesnt play a ton of man coverage theyre more conversant in two-deep stuff. One example: They have 124 pass-defense snaps in quarters, fourth-most in the league behind the Browns, 49ers, and Bills. Brady against quarters this season: 59 of 83 for 680 yards, 481 air yards, eight touchdowns, and two interceptions. So, if the Bucs can keep the pass rush at bay, Brady can hunt and hes clicking in this offense as never before.

Id say every week is getting a little bit better and a little bit more consistent [with] better communication, Brady said of the structure this week. Were all understanding each other a little bit better each week. Football season is tough theres a lot of things to coordinate, theres a lot of moving parts, different players and in and out, youre running different schemes. But I think weve just tried to not take the foot off the gas pedal [and] tried to understand each other a little bit better each week and try to put ourselves in a decent position. Any time you make the playoffs, its a good feeling and its a great opportunity to be playing this weekend. A privilege, I think, for all of us. I think we want to go make the most of it. Playoff football is pretty special to be a part of, and Ill be excited to be out there Saturday night.

Why wouldnt he?

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Anatomy of a wild-card win: The three-pronged plan that has Tampa Bays offense humming - Yahoo Sports