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Cell Biology

Good News, We Can Activate The Cells That Keep Our Muscles From Wasting Away After 30 – ScienceAlert

Unfortunately, for those of us approaching or beyond 30 years of age - this is the point our muscles start to basically shrink away. You may think you've heard it all before, but a new review presents yet another reason we really should avoid slacking off when it comes to moving our behinds.

Amongst many other things, exercise has been shown to increase mitochondria- energy-generating organelles - within cells; it also increases blood supply, waste removal, and bone strength.

While many muscle degeneration studiesfocus on much older people, the slow decline of muscle tissue in our bodies actually begins in our 30s, with an average of between three to five percent muscle loss every year.

Thankfully, our muscles are able to regenerate, so with a bit of effort on our part, we can counteract this wastage.

Muscle growth, or regeneration after injury, involves satellite cells. When they divide into a new generation of cells, they can either become more satellite cells, or myoblasts - cells which then divide into muscle cells. When they're not used however, satellite cells go into an energy-saving dormancy.

Cellular biologist William Chen and colleagues from the University of Ottawa in Canada reviewed the literature on how these cells function, including human strength training and endurance exercise studies, as well as molecular and genetic studies on mice.

"It is evident that satellite cells are activated through various signalling pathways following exercise," the team found, with multiple studies of human training sessions indicating an increase in satellite cell proliferation.

Neglecting exercise causes problems, because like all cells, satellite cells become damaged and filled with cellular trash as the normal processes of life batter them about as they age. Even while dormant, when cellular activity is reduced, the process of keeping themselves in this state still produces cellular waste.

Thus, if satellite cells stay dormant for too long, the waste build-up can cause damage, preventing the cells from dividing and replacing themselves. Even worse, in ageing muscles, if they're not activated, satellite cells can get stuck in the dormant phase and lose all ability to divide and multiply.

This means they are no longer capable of replacing defunct muscle cells with shiny new healthy ones, or making more copies of themselves.

Healthy dormancy (quiescence) requires regular activation. (Chen et al, Open Biology, 2020)

"Physical inactivity becomes more detrimental with age as satellite cells accumulate higher levels of cellular waste and DNA damage during longer periods of deep quiescence," Chen and colleagues explain in their review.

So, giving these cells a regular prod through exercise, to remind them how to be active, helps more of them retain their full function.

However, "exercise alone does not prevent all age-related defects in skeletal muscle," the team wrote.

"The satellite cell population still diminishes to some degree over age... Regardless, lifelong resistance exercise should be pursued as the effects of [age-related skeletal muscle loss] are greatly diminished when compared with sedentary lifestyles."

The researchers point out the exact mechanisms of satellite cell replacement are not yet fully understood, nor is their behaviour during exercise. They recommend more research be focused in these directions.

With skeletal muscle making up 40 percent of our body in terms of weight, it makes sense that the condition of the bulk of these cells and their makers has huge impacts on our overall health.

Muscle strength is correlated with increased quality of life, particularly as we age. So this aspect of satellite cell biology is just one of many ways exercise helps to keep our muscles and the rest of us healthy.

This review was published in Open Biology.

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Good News, We Can Activate The Cells That Keep Our Muscles From Wasting Away After 30 - ScienceAlert

Cell Biology

‘Senolytic’ therapy blunts liver tumor progression in animal models – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.May 20 2020

"Senotherapy," a treatment that uses small molecule drugs to target "senescent" cells, or those cells that no longer undergo cell division, blunts liver tumor progression in animal models according to new research from a team led by Celeste Simon, Ph.D., a professor of Cell and Developmental Biology in the Perelman School of Medicine at the University of Pennsylvania and scientific director of the Abramson Family Cancer Research Institute. The study was published in Nature Cell Biology.

This kind of therapy is not something that has been tried before with liver cancer. And in our models, so-called 'senolytic' therapy greatly reduced disease burden, even in cases with advanced disease."

Celeste Simon, Ph.D., Professor of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania

Loss of the enzyme FBP1 in human liver cells significantly increases tumor growth. Previous research has shown FBP1 levels are decreased in stage 1 tumors, and further reduced as the disease progresses. In this study, Simon and her team used RNA-sequencing data to identify FBP1 as universally under-expressed in the most common form of liver cancer, hepatocelluar carcinoma, regardless of underlying causes like obesity, alcoholism, and hepatitis.

The loss of FBP1 in liver cells activates the neighboring hepatic "stellate cells"--which make up ten percent of liver mass--causing fibrosis (tissue scarring) and subsequent stellate cell senescence, both of which promote tumor growth. Researchers found that these senescent stellate cells can be selectively targeted by senolytics, including Navitoclax (already in clinical trials for other diseases, like hematological malignancies), in order to blunt tumor progression driven by liver cell-specific FBP1 loss.

The team provides the first genetic evidence for FBP1 as a bona fide metabolic tumor suppressor in the liver and that its loss in liver cells promotes the growth of tumors because of effects on other cells within the tumor microenvironment.

Using genetically engineered mouse models, the team eliminated FBP1and found the disease progressed more rapidly and tumor burden greatly increased in carcinogen-mediated, dietary, and other forms of hepatocellular carcinoma.

"The case with liver cancer is very dire, once you get beyond a certain stage there are limited, if any, treatments available," Simon said. "As obesity rates continue to increase and viral infections continue to be a problem, there is going to be an increasing surge of liver cancer which currently has few treatment options. And since FBP1 activity is also lost in renal cancer, FBP1 depletion may be generally applicable to a number of human cancers. What's unique about our senotherapy approach is that we are specifically targeting other cells in the liver tumor environment rather than the cancer cells themselves."

Next steps, according to researchers will be to begin to test these treatments in a clinical setting.

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'Senolytic' therapy blunts liver tumor progression in animal models - News-Medical.Net

Cell Biology

Assessing the Fallout From the Coronavirus Pandemic Cell Biology Cloud Computing Market 2020: Global Size, Supply-Demand, Product Type and End User…

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Assessing the Fallout From the Coronavirus Pandemic Cell Biology Cloud Computing Market 2020: Global Size, Supply-Demand, Product Type and End User...

Cell Biology

Cell biologist to study coronavirus-related infection of respiratory cells – UC Riverside

Prue Talbot, a professor of cell biology at UC Riverside, has received a seed grant to study the COVID-19-related infection of respiratory cells.

She and her team will use the funds to test the hypothesis that electronic cigarettes and nicotine increase the ACE2 receptor on respiratory epithelium, providing more binding sites for the virus and increasing the possibility of infection.

We expect our work will help clarify if the use of tobacco products makes it more likely for an infection to occur, Talbot said.

Angiotensin converting enzyme-2, or ACE2, is a special receptor on some cells that has attracted the attention of drug companies as a potential target for addressing the novel coronavirus.

The $25,000, six-month grant from the California Tobacco-Related Disease Research Program of the University of California will support the research of three graduate students.

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Cell biologist to study coronavirus-related infection of respiratory cells - UC Riverside

Cell Biology

Paying the Price of Protection – Newswise

Newswise Is the wanton killing of cells in autoimmune disease a case of mistaken identity, or does it arise from an important physiological service? The first is the commonly accepted view that autoimmune attack is a sort of mistake. But the latter view may be closer to the truth, according to a new model proposed by researchers at the Weizmann Institute of Science. Among other things, the model suggests a solution to the long-standing riddle of why some organs are susceptible to autoimmune diseases while others are not. The findings were published in the journal Immunity.

Yael Korem Kohanim, a doctoral student in the lab of Prof. Uri Alon in the Institutes Department of Molecular Cell Biology, who led the study, explains that autoimmune diseases can be divided into two types systemic ones like lupus that attack many organs in the body, and those like type 1 diabetes that affect just one organ. One of the riddles about this second, organ-specific type of autoimmune disease is why some organs get autoimmune diseases while others do not. The pancreas is an extreme example: the insulin-producing beta cells that make up 2-4% of the pancreas are highly prone, while the rest of the pancreas almost never gets an autoimmune disease.

Likewise, Hashimotos thyroiditis affects the thyroids of some 7% of the population, whereas the parathyroid glands right next to them are rarely affected by autoimmune syndromes. These organ-specific autoimmune diseases tend to follow a similar pattern, arising in children or young adults (unlike genetic diseases that appear at birth, or those of aging), and they involve the destruction of cells that secrete essential hormones. Immune cells called T cells somehow identify these endocrine cells as dangerous and eradicate them on contact.

Korem Kohanim, Prof. Alon, and the research group, including Dr. Avichai Tendler, Dr. Avi Mayo, and Prof. Nir Friedman in the Department of Immunology, asked: What if the T cells are meant to kill these cells all along?

Keeping supply matched to demand

The researchers hypothesized that T cells might be kept on the payroll as an extra layer of protection to ensure that hormone levels stay within narrow limits. Hormones insulin, thyroid, cortisol tend to function in feedback loops; too little is as harmful as too much. When demand for the hormone rises for example, a demand for insulin when glucose is repeatedly sensed the cells not only step up production, they ramp up cell division to help meet that demand. But cell division carries risks, as a certain percentage of the new cells are likely to carry mutations. Most such mutations are harmless, but if one disrupts the cells delicate sensing machinery, the cell will misread the demand as high when it is actually low. The result is deadly: the cell will continue not only to pump out extra hormones, it will divide again and again to produce new cells with the same mutation, which will then divide again and produce even more of the hormone, soon causing severe disease.

T cells, which select their targets by recognizing small pieces of proteins that identify the cells they are meant to kill, could conceivably target the over-secreting cells in healthy organs. They act, in this case, as secret agents, removing cells that threaten to take over the organ and secrete too much hormone. In autoimmune diseases, the T cells might be primed to accomplish the same task but get overzealous, killing off non-mutant cells.

Was this hypothesis reasonable? Korem Kohanim, Prof. Alon, and the team delved into the literature and bioinformatics data on several single-organ autoimmune diseases, then creating a mathematical model for the functioning of healthy organs in which small numbers of T cells kept a low profile. In this model, the organs stay fit and productive as long as the T cells have a means of being highly selective, so that most of their targets would be the mutated cells.

This result agrees with the findings from research on the diseases showing that, in each one, the T cells identify proteins specifically connected to the production or secretion of the target cells hormones. In healthy organs, those T cells could use the same identification codes to target any cells that are overproducing the hormones. In other words, autoimmune diseases could be the result of a tradeoff: a layer of regulation preventing diseases linked to overproduction, while risking the opposite effect reduced production in some people.

The glands that refuse to pay the price

If other glands are not susceptible to autoimmune disease, does this mean they also forgo T-cell protection? The team went back to the literature and found that the parathyroid, for example, is highly prone to noncancerous growths called adenomas that are common in post-menopausal women, affecting as many as one in 50. These adenomas secrete huge amounts of hormone, causing a disease called hyperparathyroidism. Other examples, though less dramatic than parathyroid adenomas, supported the idea that a lack of T-cell intervention, as the model would suggest, could result in unchecked hormone secretion and cell growth.

The model explains a number of puzzling findings, says Korem Kohanim. For example, we looked at genetic sequences of T cells found in healthy people, and noted that some of them indeed have the exact same protein-identifying receptors as the T cells found in those with autoimmune diseases. The explanation has always been that the apparently healthy people have a mild form of the disease, or one in its initial stages. But the findings are more logical if you assume these auto-reactive T cells are meant to be there; that they are meant to keep us from getting diseases of cell division and hormone overproduction.

So far, says Korem Kohanim, the model provides a solution to a riddle that has long plagued researchers, though experimentation is needed to see if its claims are borne out. However, it has already garnered interest in the field and is generating discussion among top immunologists. The Alon lab will continue to collaborate on the project with the Friedman lab as they develop means of experimentally testing the models results.

We think that autoimmune diseases do not come out of nowhere. They are a malfunction, but one of a physiological system that is already in place, Korem Kohanim says.

We follow in the footsteps of pioneers at Weizmann Irun Cohen and Michal Schwartz and their students who emphasized the immune system as tending our bodies as well as fighting pathogens, Prof. Alon says, adding: I cant wait to see if this theory is fruitful in the sense of generating new experiments that will teach us about the mysteries of autoimmune diseases.

Prof. Uri Alons research is supported by the Sagol Institute for Longevity Research; the Jeanne and Joseph Nissim Center for Life Sciences Research; the Braginsky Center for the Interface between Science and the Humanities; the Kahn Family Research Center for Systems Biology of the Human Cell; the Zuckerman STEM Leadership Program; the Rising Tide Foundation; the estate of Olga Klein Astrachan; and the European Research Council. Prof. Alon is the incumbent of the the Abisch-Frenkel Professorial Chair.

Prof. Nir Friedmans research is supported by the David and Fela Shapell Family Institute for Preclinical Studies; the Dr. Dvora and Haim Teitelbaum Endowment Fund; the Pearl Welinsky Merlo Foundation for Scientific Progress Research Fund; the Florence Blau, Morris Blau, and Rose Peterson Fund; the Rising Tide Foundation; the Park Avenue Charitable Fund; Gertrude Comninos; the estate of Robert Einzig; and the estate of Emile Mimran. Prof Friedman is the incumbent ofthe Eugene and Marcia Applebaum Professorial Chair.

The Weizmann Institute of Science in Rehovot, Israel, is one of the worlds top-ranking multidisciplinary research institutions. The Institutes 3,800-strong scientific community engages in research addressing crucial problems in medicine and health, energy, technology, agriculture, and the environment. Outstanding young scientists from around the world pursue advanced degrees at the Weizmann Institutes Feinberg Graduate School. The discoveries and theories of Weizmann Institute scientists have had a major impact on the wider scientific community, as well as on the quality of life of millions of people worldwide.

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Paying the Price of Protection - Newswise

Cell Biology

Superpower Discovered in Squids: They Can Massively Edit Their Own Genetics – SciTechDaily

Revealing yet another super-power in the skillful squid, scientists have discovered that squid massively edit their own genetic instructions not only within the nucleus of their neurons, but also within the axon the long, slender neural projections that transmit electrical impulses to other neurons. This is the first time that edits to genetic information have been observed outside of the nucleus of an animal cell.

The study, led by Isabel C. Vallecillo-Viejo and Joshua Rosenthal at the Marine Biological Laboratory (MBL), Woods Hole, is published this week in Nucleic Acids Research.

The longfin inshore squid, Doryteuthis pealeii, long established as a research organism for fundamental biological studies. Credit: Elaine Bearer

The discovery provides another jolt to the central dogma of molecular biology, which states that genetic information is passed faithfully from DNA to messenger RNA to the synthesis of proteins. In 2015, Rosenthal and colleagues discovered that squid edit their messenger RNA instructions to an extraordinary degree orders of magnitude more than humans do allowing them to fine-tune the type of proteins that will be produced in the nervous system.

But we thought all the RNA editing happened in the nucleus, and then the modified messenger RNAs are exported out to the cell, says Rosenthal, senior author on the present study. Now we are showing that squid can modify the RNAs out in the periphery of the cell. That means, theoretically, they can modify protein function to meet the localized demands of the cell. That gives them a lot of latitude to tailor the genetic information, as needed. The team also showed that messenger RNAs are edited in the nerve cells axon at much higher rates than in the nucleus.

Top, schematic of squid anatomy showing the location of the giant axon, an unusually large neural projection that partly controls the squids jet propulsion system, used for very fast movement, attacks and escapes. Below, schematic of a neuron, showing the location of the nucleus where all RNA editing was previously thought to occur, and the axon, where local RNA editing was identified in squid. Credit: Vallecillo-Viejo et al, Nucl. Acids Res., 2020.

In humans, axon dysfunction is associated with many neurological disorders. Insights from the present study could accelerate the efforts of biotech companies that seek to harness this natural RNA editing process in humans for therapeutic benefit.

Scientists from Tel Aviv University and The University of Colorado at Denver collaborated with MBL scientists on the study.

Previously, Rosenthal and colleagues showed that octopus and cuttlefish also rely heavily on mRNA editing to diversify the proteins they can produce in the nervous system. Together with squid, these animals are known for strikingly sophisticated behaviors, relative to other invertebrates.

Reference: Spatially regulated editing of genetic information within a neuron by Isabel C Vallecillo-Viejo, Noa Liscovitch-Brauer, Juan F Diaz Quiroz, Maria F Montiel-Gonzalez, Sonya E Nemes, Kavita J Rangan, Simon R Levinson, Eli Eisenberg and Joshua J C Rosenthal, 23 March 2020, Nucleic Acids Research.DOI: 10.1093/nar/gkaa172

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Superpower Discovered in Squids: They Can Massively Edit Their Own Genetics - SciTechDaily

Cell Biology

Novel insights on SARS-CoV-2 cell entry may inform further vaccine and treatment development – News-Medical.Net

A research group from Harvard Medical School reported two cryo-electron microscopy structures derived from a single preparation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein in their paper available on the preprint server bioRxiv*. Understanding the nuances of prefusion and postfusion conformations shed light on viral cell entry and may, in turn, guide the development of vaccines and drugs.

Novel Coronavirus SARS-CoV-2 Colorized scanning electron micrograph of a VERO E6 cell (purple) exhibiting elongated cell projections and signs of apoptosis, after infection with SARS-COV-2 virus particles (pink), which were isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

The current pandemic of coronavirus disease 2019 (COVID-19) reached nearly every corner of our planet. Due to its high case-fatality rate and catastrophic economic and social repercussions, both SARS-CoV-2 and COVID-19 became the top research priority of scientists around the world.

Membrane fusion represents a pivotal early step for all enveloped viruses in order to enter host cells and establish the infection. Albeit this is an energetically favorable process, there are high kinetic barriers when two membranes approach each other before fusion, primarily due to hydration repulsive forces.

The fusion protein for coronaviruses is the S-protein that decorates the surface of the viral particle as an extensive crown, which is how these viruses were named in the first place. The protein also instigates the neutralizing antibody response, which makes it an important target in vaccine development endeavors.

In short, the viral S-protein forms a trimer and catalyzes fusion between viral and target cell membranes, which is the first step of infection. This is why a research group decided to appraise distinct conformational states of SARS-CoV-2 S-protein in order to further inform the development of vaccines and therapeutics.

In this study, a fully wild-type form of SARS-CoV-2 S-protein was expressed in human embryonic kidney 293 (HEK-293) cells, which are widely used in cell biology research. Cryogenic electron microscopy was then used to derive two structures representing S-protein's prefusion and postfusion states both derived from a single preparation previously solubilized in detergent.

The cell-cell fusion assay was utilized to quantify the fusion activity mediated by SARS-CoV-2 S-protein. Structure determination was carried out by rounds of three-dimensional classification, refinement, and masked local refinement. All experiments were performed with a Biacore 3000 system, which is used for real-time biomolecular interaction analysis by surface plasmon resonance technology.

This study has identified a structure in the vicinity of the fusion peptide called the fusion peptide proximal region (FPPR), which prompts the fusogenic structural rearrangements of S-protein. Nonetheless, certain questions are open regarding membrane fusion, since the regions near the viral membrane are still not evident in the reconstructions even in the structures obtained by the Harvard authors with a full-length S construct.

It has been shown how spontaneous structural transformation to the postfusion state under mild conditions is independent of target cells. The prefusion trimer (3.1-Angstrom resolution) forms a steadfastly packed structure with three receptor-binding domains, substantially different from recently published structures of a stabilized S-ectodomain trimer.

Conversely, the postfusion conformation (3.3-Angstrom resolution) is a robust tower-like trimer decorated by N-linked glycans (i.e., oligosaccharides attached to a nitrogen atom) along its long axis with more or less even spacing suggesting a possible association with mechanism protecting the virus from unfavorable external conditions and host immune responses.

Whether other viral proteins (such as M-protein) may aid in stabilizing the spike by interacting with the heptad repeat 2 remains an intriguing question. "We still need a high-resolution structure of the intact S-protein in the context of the membrane and other viral components to answer the various open questions," explain study authors.

The most unanticipated finding from the current study is the notion that the kinetic barrier for the conformational transition relevant for viral entry is surprisingly low for this S-protein. Hence, further investigation is needed to elucidate whether this observation relates directly to successful membrane fusion or infection, and perhaps effective human-to-human transmission.

A model for structural rearrangements of SARS-Cov-2 S protein. (A) Structural changes independent of a target cell. We suggest that both the prefusion and postfusion spikes are present on the surface of mature virion and the ratio between them may vary (diagram of virion). The postfusion spikes on the virion are formed by S2 after S1 dissociates in the absence of ACE2. (B) ACE2-dependent structural rearrangements. Structural transition from the prefusion to postfusion conformation inducing membrane fusion likely proceeds stepwise as follows: 1) FPPR clamps down RBD through CTD1 in the prefusion S trimer, but it occasionally flips out of position and allows an RBD to sample the up conformation. 2) RBD binding to ACE2 creates a flexible FPPR that enables exposure of the S2 cleavage site immediately upstream of the adjacent fusion peptide (FP). Cleavage at the S2 site, and perhaps also the S1/S2 site, releases the structural constraints on the fusion peptide and initiates a cascade of refolding events in S2, probably accompanied by complete dissociation of S1. 3) Formation of the long central three-stranded coiled-coil and folding back of HR2. 4) Formation of the postfusion structure of S2 that brings the two membranes together, facilitating formation of a fusion pore and viral entry.

It seems that a safe and effective vaccine represents the only viable option to reduce or eliminate the threat of SARS-CoV-2 adequately. The early round of vaccine candidates played with various forms of the S-protein, primarily inspired and modeled on those designed against the original SARS-CoV and MERS-CoV viruses.

However, some sobering insights surfaced from the development of SARS-CoV vaccines, suggesting that certain S-protein-based immunogens generate harmful immune responses to lungs or liver in animal models, as well as an immune enhancement or antibody-dependent enhancement of infectivity that makes the infection even more acute.

"It will be critical to define structural determinants that distinguish the ineffective or deleterious responses from the protective responses, to refine next-generation vaccine candidates," caution study authors. "Refined immunogens will be particularly critical if SARS-CoV-2 becomes seasonal and returns with antigenic drift, as do influenza viruses", they add.

Even though virus-encoded enzymes (such as proteases or RNA-dependent RNA polymerase) are outstanding therapeutic targets, fusion inhibitors that inhibit conformational changes of S-protein may also be budding drug candidates. Such fusion inhibitors may even be superior, as (akin to antibodies) they do not need to cross cell membranes in order to reach their target.

Furthermore, S-protein functions uniquely without any obvious cellular homologs, making it a more probable target for highly specific inhibitors with fewer side effects when compared to viral enzyme inhibitors. For example, the same research group has recently identified several small-molecule fusion inhibitors against HIV envelope spike, which was guided by a neutralizing antibody.

"Our work, which represents one of many complementary studies, may guide our responses to the spread of SARS-CoV-2 in a more rational way than would have been possible even a few months ago", conclude study authors. These insights may prove very useful for combined strategy in developing both the vaccine and an efficacious drug.

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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Novel insights on SARS-CoV-2 cell entry may inform further vaccine and treatment development - News-Medical.Net

Cell Biology

Agilex Biolabs Presents the Australian Advantage, including the World’s Largest Rebate on Clinical Trial Spend, at BIO Korea 2020 – Business News Asia

Agilex Biolabs, Australias largest specialist bioanalytical laboratory for biotech clinical trials, is presenting the Australian Advantage including the worlds most attractive rebate on clinical trials costs, at BIO Korea 2020.

The presentation by Kurt Sales (B.Sc; B.Sc (MED) Hons; M.Sc, Ph.D, PGCM)Director, Immunoassay at Agilex Biolabs, also detailed how well the Australian clinical trials industry had managed during the COVID-19 crisis with most sites, CROs, and labs including Agilex Biolabs, staying open.

The presentation is at 13.50 on Friday 22, May 2020 via the virtual conference platform.https://www.biokorea.org/index.asp

Agilex Biolabs also launched a News Video Update on the COVID-19 impact on clinical trials in Australia. Watch here.https://youtu.be/vZuHAYZ-GiE

Agilex Biolabs specializes in bioanalysis of small molecules and biologics for PK, immunogenicity, biomarkers and immunological pharmacodynamics assessments.

Agilex Biolabs, the only FDA-inspected lab of its type in the region, is located in Adelaide, South Australia in a science and biotech specialist hub.

Agilex Biolabs CEO Jason Valentine said: Aglilex Biolabs has just expand its labs by more than 30% to accommodate biotech demand from APAC and the USA.

He said more than 38% of Agilex Biolabs biotech clients already come from the APAC region primarily from China and South Korea.

APAC clients are particularly attracted by Agilex Biolabs FDA-inspected status, and the more than 40% rebate on clinical trial spend that applies in Australia, he said.

Our world-class bioanalytical facilities have OECD GLP Recognition with NATA (Australian Government OECD GLP Compliance monitoring authority) and ISO 17025 Accreditation for global recognition.

Agilex Biolabs specialises in bioanalysis of small molecules and biologics for PK, immunogenicity, biomarkers and immunological pharmacodynamics assessments utilising LC-MS/MS, immunoassay (Mesoscale, Gurolab, Luminex) and flow cytometry (BD FACSymphony A3, 20 colour cell analyser).

Agilex also offers pharmacodynamics services that include immunobiology services using the latest state-of-the-art technology to support immunology, cell biology and mode of action assays, including: Immunophenotyping Receptor occupancy Cytokine release assays (whole blood or PBMC stimulation assays) and cytokine/biomarker profiling PBMC assays and cellular mechanism of action assays (eg: ADCC)

The FDA-inspected facilities have more than 65 dedicated laboratory staff, and annually support more than 80 clinical trials. This year they will analyse more than 60,000 samples for pharma/biotechs from US, Europe and APAC.

Please Book a Briefing with us before you start your next clinical trial.https://calendly.com/agilexbiolabs/15min

Australia: +61 8 8302 8777 | China: +86 21 8036 9483 | South Korea: +82 80 812 1255 | USA: +1 800 247 1909

About Agilex Biolabshttps://www.agilexbiolabs.com/

Agilex Biolabs, Australias leading bioanalytical laboratory, has more than 20 years experience in performing regulated bioanalysis, including quality method development, method validation and sample analysis services. We have successfully supported hundreds of preclinical and clinical trials around the world where customers choose Australia for the streamlined regulatory process and access to the worlds most attractive R&D rebate of more than 40% on clinical trial work conducted in Australia.

We offer services for both small molecules and biologics for PK, immunogenicity (PD) and biomarker bioanalysis utilising the two platforms of LC-MS/MS and Immunoassay.

Agilex Biolabs operates a fully quality-assured laboratory ensuring that, within the principles of GLP, assays are validated to the latest FDA/EMA guidance and study samples are assayed and reported to the sponsors desired format using WATSON LIMS. Laboratory certifications include OECD GLP and ISO/IEC17025.

Our highly experienced team consists of over 65 dedicated laboratory staff with over 15 years average industry experience across senior scientists. Expertise includes development of robust compliant PK and PD assays de novo or by method transfer.

Our laboratory is fitted with 7 SCIEX tandem mass spectrometers, 6 API 4000 and 1 QTRAP 5500 as our standard platform for LC-MS/MS analysis. For immunoassay, we employ the state-of-the-art systems of Meso Scale Discovery (MSD) and Gyrolab xPlore.

Agilex Biolabs owns a suite of validated biosimilar assays that have already supported biosimilar studies executed in the region. These assays include Avastin/Bevacizumab, Lucentis/Ranibizumab, Actemra/Tocilizumab, Xolair/Omalizumab, Herceptin/Trastuzumab and Solaris/Eculizumab. We would like to discuss how we can support companies with biosimilar pipelines looking to conduct trials in the region. Our validated biosimilar assays require less setup saving time and money.

Agilex Biolabs also have a suite of biomarker assays that have been developed to support studies in the areas of endocrinology (estrone, estradiol, progesterone, testosterone and others).

Recently, Agilex Biolabs has added a comprehensive cannabinoid assay to its suite of validated assays to support clinical trials. The fully validated assay includes the five cannabinoids THC, CBD, CBN and the two THC-metabolites OHTHC and COOHTHC.

Our LC-MS/MS experience includes NCEs, sugars, nucleotides, enantiomers, steroids, prodrugs, peptides, immunosuppressants, nanoparticles, neurotransmitters, oligonucleotides and polymeric mixtures.

Our biologics experience entails PK analysis using colorimetric, fluorescence or chemiluminescence detection for recombinant or fusion proteins, monoclonal antibodies, ADCs, immunogenicity testing, biomarker analysis and PBMC blood stimulation assays.

See us featured in Endpointshttps://tinyurl.com/uqmkzcu

Media Contact:Kate NewtonMedia@AgilexBiolabs.com

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Agilex Biolabs Presents the Australian Advantage, including the World's Largest Rebate on Clinical Trial Spend, at BIO Korea 2020 - Business News Asia

Cell Biology

Scaffold Technology Market 2020 With COVID-19 Impact Analysis, Business Opportunities and Future Outlook 2026 – Cole of Duty

The Global Scaffold Technology Market report is a comprehensive analysis of different market factors and conditions that can decide the growth of the market. The Scaffold Technology report is a valuable source of information to different individuals and organizations that are interested in either entering the Scaffold Technology industry or in identifying new and innovative methods of increasing the revenue earned. These trends are categorized based on their popularity and are presented in the report. The Scaffold Technology market is further divided into different market segments.

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Scaffold Technology Market is anticipated to grow at a CAGR of 10.37% from 2019 to 2026

Scaffold Technology is primarily tissue engineering, evolving into biological alternatives, with applications for replacing, regenerating and repairing diseased or defective organs or tissues.Key factors such as the increase in medical expenditures, the improvement of the medical system, and the increase in R&D investment account for a large proportion in North America. As healthcare organizations continue to increase their understanding of this technology, companies in the Asia Pacific region are expected to drive industry expansion in the future

The prominent players are

NuVasive, 3D Biomatrix, Akron Biotech, Arterial Remodeling Technologies S.A., Matricel, Molecular Matrix, Nanofiber Solutions, ReproCELL

Scaffold Technology Breakdown Data by TypeCell Attachment and MigrationNutrients and Products DiffusionCell Phase Behavior ModificationOther

Scaffold Technology Breakdown Data by ApplicationPharmaceuticalsResearch Laboratories and InstitutesHospitalsDiagnostic CentersOther

Scaffold Technology seeks a persistent evolution of technology with dependence on cellular biology that brings to the fore biological substitutes for regenerative action by taking on diseased organs or tissues. This technology also brings to the fore in vivo and in vitro tissue regeneration within synthetic polymeric scaffolds. scaffold technology is divided into drug development, stem cell research, cancer, tissue engineering and clinical application and others

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Scaffold Technology Market 2020 With COVID-19 Impact Analysis, Business Opportunities and Future Outlook 2026 - Cole of Duty

Cell Biology

Genespire and SR-Tiget announce strategic alliance for the development of transformative gene therapies for genetic diseases and disclose collaboratio…

Pre-clinical data from SR-Tiget, included in the alliance with Genespire, to be presented at ASGCT 23rd Annual Meeting

Italy, Milan, 13 May 2020: The San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), one of the worlds leading gene therapy research institutes jointly managed by Fondazione Telethon and Ospedale San Raffaele and Genespire, a gene therapy company developing transformative therapies for genetic diseases, and spin-out of SR-Tiget, announced today their alliance on the research and development of candidate therapeutic products for people affected by primary immunodeficiencies and metabolic diseases based on novel gene editing and lentiviral vector technologies developed by SR-Tiget.

Genespire was co-founded in March 2020 by SR-Tiget director and gene therapy pioneer Prof. Luigi Naldini and Dr. Alessio Cantore, Fondazione Telethon and Ospedale San Raffaele. Genespire recently raised 16 million in a Series A financing round from Sofinnova Partners.

Under the terms of the alliance, Genespire and SR-Tiget will study and further develop novel gene therapies, which have the unique potential to address severe unmet medical need and exploit gene editing and lentiviral vector technologies developed by SR-Tiget.

Genespire was granted an exclusive global license for the research, development and commercialization of gene therapies for metabolic diseases based on SR-Tigets alloantigen free, microRNA-regulated lentiviral vectors, which allow for stable liver gene therapy even for diseases with early onset, requiring administration at a young age.

Genespire was also granted exclusive licenses and options to the results of a joint research and development program with SR-Tiget in the T-cell and Hematopoietic Stem Cells field to address genetic diseases, in particular primary immunodeficiencies, exploiting the ex vivo gene editing technology. SR-Tiget and Genespire will first collaborate to bring an ex-vivo autologous edited T-cell gene therapy for X-linked Hyper IgM syndrome (HIGM1) to the clinic, which becomes Genespires lead candidate product. HIGM1 is caused by inherited mutations of the CD40 ligand gene (CD40L), resulting in impaired antibody response and innate immunity, meaning that people find it difficult to fight off infections and eventually succumb to them. The treatment objective is to correct the defective gene through targeted editing of the endogenous locus, thereby maintaining physiological regulation of the CD40L gene, with the aim of improving the immune response of the patients.

Preclinical results of SR-Tiget on HIGM1 will be disclosed in an oral presentation at the American Society for Cell and Gene Therapy (ASGCT) 23rd Annual Meeting, taking place virtually from 12-15 May 2020 by SR-Tiget (details of Presentation 1 below). The presentation will outline the technology and its preclinical validation in the disease model and patient derived cells and discuss the potential of the gene edited T-cell treatment approach for patients with Hyper IgM.

Dr. Alessio Cantore will also present novel data related to the potential of the lentiviral vector platform for liver gene therapy in an oral presentation at ASGCT (details of Presentation 2 below). The presentation will focus on investigating the stability of lentiviral vector genetically modified liver cells following post-natal liver growth in mice, in view of its potential application to pediatric patients.

Luigi Naldini, Director of SR-Tiget and scientific co-founder of Genespire said: We are excited to have secured a path for bringing forward some of the gene therapy work pioneered at SR-Tiget to eventually help individuals affected by severe metabolic and immunodeficiency disorders. SR-Tigets alliance with Genespire will provide the means to progress effectively to clinical trials, with a strong view to develop efficacious and safe medicines ready for market access.

Julia Berretta, Chief Executive Officer of Genespire commented: SR-Tiget brings outstanding expertise and significant experience in developing gene therapies from bench to bedside. We believe that our strong partnership with SR-Tiget, led by internationally recognized experts Prof. Luigi Naldini and Dr. Alessio Cantore will be fundamental for Genespire to carry out its goal of translating pioneering science into transformative therapeutic solutionsfor patients.

-ENDS-

Oral presentation 1 details:

Title:

Modeling, Optimization and Comparative Efficacy of HSC- and T-cell Based Editing Strategies for Treating Hyper IgM Syndrome

Authors:

Valentina Vavassori, Elisabetta Mercuri, Genni Marcovecchio, Maria Carmina Castiello, Giulia Schiroli , Luisa Albano, Elena Fontana, Andrea Annoni, Valentina Capo, Carrie Margulies, Frank Buquicchio, Joseph Kovacs, Eugenio Scanziani, Cecilia Cotta-Ramusino, Anna Villa, Luigi Naldini, Pietro Genovese

Date and time: May 14th 2020, 3:45 PM EDT

Session: 354 Gene Therapies for Hemophilia and Immune Disorders

Abstract #937

Oral Presentation 2 Details

Title:

Investigating the stability of lentiviral vector targeted liver cells during post-natal growth for in vivo gene therapy applications

Authors:

Michela Milani, Francesco Starinieri, Cesare Canepari, Tongyao Liu, Federica Moalli, Gioia Ambrosi, Tiziana Plati, Mauro Biffi, Cesare Covino, Timothy Nichols, Matteo Iannacone, Robert Peters, Luigi Naldini, Alessio Cantore

Date and time: May 14th 2020, 4:15 pm EDT

Session: 350 RNA Virus Vectors

Abstract #911

About Hyper IgM Syndrome (HIGM)

Hyper IgM is a Primary Immune Deficiency affecting 1:250,000-500,000 patients. The disease is linked to mutations in the CD40L gene, which is expressed in activated CD4 T cells, and results in impaired antibody production and innate immunity. The current standard of care is constituted by continuous Ig replacement, and antibiotic-antifungal prophylaxis, but the disease is still linked to high morbidity and reduced life expectancy. Allogeneic hematopoietic stem cell transplant (HSCT) is potentially curative, but is limited by matched donor availability and is associated with high risk of graft versus host disease, infections and death. Thus, improved therapeutic alternatives are strongly needed.

About Genespire

Genespire is a biotechnology company focused on the development of transformative gene therapies for patients affected by genetic diseases, particularly primary immunodeficiencies and inherited metabolic diseases. Based in Milan, Italy, Genespire was founded in March 2020 by the gene therapy pioneer Prof. Luigi Naldini and Dr. Alessio Cantore, Fondazione Telethon and Ospedale San Raffaele. It is a spin-off of SR-Tiget, a world leading cell and gene therapy research institute and is backed by Sofinnova Partners. http://www.genespire.com

About SR-Tiget

Based in Milan, Italy, the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) is a joint venture between the Ospedale San Raffaele and Fondazione Telethon. SR-Tiget was established in 1995 to perform research on gene transfer and cell transplantation and translate its results into clinical applications of gene and cell therapies for different genetic diseases. Over the years, the Institute has given a pioneering contribution to the field with relevant discoveries in vector design, gene transfer strategies, stem cell biology, identity and mechanism of action of innate immune cells. SR-Tiget has also established the resources and framework for translating these advances into novel experimental therapies and has implemented several successful gene therapy clinical trials for inherited immunodeficiencies, blood and storage disorders, which have already treated >115 patients and have led through collaboration with industrial partners to the filing and approval of novel advanced gene therapy medicines.

About Fondazione Telethon

Fondazione Telethon is a non-profit organisation created in 1990 as a response to the appeals of a patient association group of stakeholders, who saw scientific research as the only real opportunity to effectively fight genetic diseases. Thanks to the funds raised through the television marathon, along with other initiatives and a network of partners and volunteers, Telethon finances the bestscientific research on rare genetic diseases, evaluated and selected by independent internationally renowned experts, with the ultimate objective of making the treatments developed available to everyone who needs them. Throughout its 30 years of activity, Fondazione Telethon has invested more than 528 million in funding more than 2.630 projects to study more than 570 diseases, involving over 1.600 scientists. Fondazione Telethon has made a significant contribution to the worldwide advancement of knowledge regarding rare genetic diseases and of academic research and drug development with a view to developing treatments. For more information, please visit:www.telethon.it

About Ospedale San Raffaele

Ospedale San Raffaele (OSR) is a clinical-research-university hospital established in 1971 to provide international-level specialised care for the most complex and difficult health conditions. OSR is part ofGruppo San Donato, the leading hospital group in Italy. The hospital is a multi-specialty center with over 60 clinical specialties; it is accredited by the Italian National Health System to provide care to both public and private, national and international patients. Research at OSR focuses on integrating basic, translational and clinical activities to provide the most advanced care to our patients. The institute is recognized as a global authority in molecular medicine and gene therapy, and is at the forefront of research in many other fields. Ospedale San Raffaele is a first-class institute which treats many diseases and stands out for the deep interaction between clinical and scientific area. This makes the transfer of scientific results from the laboratories to the patients bed easier. Its mission is to improve knowledge of diseases, identify new therapies and encourage young scientists and doctor to grow professionally. For more information, please visit:www.hsr.it

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Genespire and SR-Tiget announce strategic alliance for the development of transformative gene therapies for genetic diseases and disclose collaboratio...