Category Archives: Cell Biology

Cell Biology

Nearly $3 Million Awarded to Study Sickle Cell Disease at UConn Health – UConn Today – UConn

In honor of World Sickle Cell Day, marked each June 19, we share that UConn Healths Dr. Marja Hurley has recently received nearly $3 million in research funding from the NIH and a pharmaceutical company to advance scientific knowledge about sickle cell disease and its related bone loss.

Hurley, a pioneering physician-scientist, is renowned for her three decades of NIH-funded bone research. She is a UConn Board of Trustees Distinguished Professor of Medicine and Orthopedic Surgery at UConn Health.

Sickle cell disease is a painful inherited red blood cell condition impacting the bloods circulation due to abnormally hook-shaped red blood cells. Individuals born with the disease have severe pain episodes due to blockages that can form inside their smaller blood vessels, capillaries, and even bone marrow, when their abnormally shaped cells cannot pass through smoothly. The dangerous blockages can reduce blood flow, may cause deadly blood infections, or profound anemia, an unhealthy level of oxygen-rich red blood cells.

While the sickling of red blood cells inside bone marrow causes severe bone pain episodes it also can cause bone infarctions or damaged areas. However, little is known why a high prevalence of sickle cell patients also experience musculoskeletal frailty and brittle and broken bone complications such as osteoporosis.

To study this phenomena The National Institute of Diabetes and Digestive and Kidney Diseases has awarded a4-year $2,211,239 grantto Hurley as principal investigator with co-investigators Dr. Liping Xiao, assistant professor of medicine and psychiatry, and Siu-Pok Yee, Ph.D, associate professor of cell biology at UConn School of Medicine.

Together the research team will study how sickle cell disease contributes to impaired bone mineralization. Specifically, the researchers will research in mouse models the molecular mechanism impacting the phosphate regulating hormone Fibroblast Growth Factor 23 (FGF23). These studies will aim to identify whether FGF23 is a novel contributor to the pathogenesis of sickle cell disease-related bone loss and anemia and if it can be prevented in the laboratory with the findings translated someday to patient care.

Our hope is that we can develop a useful therapy to prevent bone loss in sickle cell disease patients in the very near future, stresses Hurley. There is much needed intervention to further fuel scientific discoveries to not only curb the pain suffered by sickle cell patients but further enhance their overall musculoskeletal health and well-being.

In addition, the pharmaceutical company, Global Blood Therapeutics(GBT), has provided Hurley with a3-year $535,000 grantto study bone and muscle function in sickle cell disease mouse models.

The drug Voxelotor is a currently FDA-approved drug for treatment for the anemia caused by sickle cell disease. However, little has been determined about the efficacy of the drug to also increase muscle strength and bone mineral density in sickle cell disease patients or mouse models. Hurleys research will be investigating this drugs promise further.

More than 3.5 million are affected worldwide by sickle cell disease, including approximately 100,000 Americans, and in Connecticut, at least 1,000 adults and 600 children. African-Americans and Latinos are predominantly affected in the U.S., with life expectancy for the majority of people with sickle cell disease is now age 40 or greater thanks to advanced health management.

Read this article:
Nearly $3 Million Awarded to Study Sickle Cell Disease at UConn Health - UConn Today - UConn

Cell Biology

Different Forms of Autism Have Opposite Problems with Brain Precursor Cells – The Scientist

The primordial cells that give rise to most other brain cells do not proliferate in a typical way in autistic peopleand that could explain how common traits emerge from a range of genetic origins, according to a new study.

The idea that autism disrupts the proliferation of neural precursor cells isnt new, but until now, few studies had investigated how that difference arises.

In the new study, scientists fashioned neural precursor cells out of cord blood cells from five autistic boys ages 4 to 14 and, to serve as controls, either their non-autistic brothers or unrelated non-autistic people. Three of the autistic children have idiopathic cases, in which there is no known genetic cause for their autism; the other two have deletions in 16p11.2, a chromosomal region linked to autism and other neuropsychiatric conditions. Three of the autistic children havemacrocephaly, or a large head.

Neural precursors from the autistic boys all proliferated in atypical ways, the scientists found. Among children with macrocephaly, this growth was accelerated, leading to 28 to 55 percent more cells than in the non-autistic controls after six days. In contrast, cells from the other two boys, both with idiopathic autism, grew more slowly and more of those cells died, yielding 40 to 65 percent fewer cells than in controls after six days.

Despite the fact that these individuals are genetically distinct, especially the idiopathic individuals, it is amazing they have a common developmental process dysfunctioncontrol of proliferation, says study co-lead investigator Emanuel DiCicco-Bloom, professor of neuroscience, cell biology and pediatrics at Rutgers University in Piscataway, New Jersey.

This overlap suggests this issue with proliferation control is a common and generalizable mechanism in autism, he adds.

The gene MAPK3, which encodes an enzyme important in brain growth and development, lies within 16p11.2. Exposed to less of the enzymes active form, phosphorylated ERK1 (P-ERK1), neural precursors in the two boys with 16p deletions proliferated more, the scientists found. The opposite held true in boys with more P-ERK1.

Exposing highly prolific precursors to basic fibroblast growth factor (bFGF), which stimulates the ERK pathway, led to a 15 to 30 percent reduction in DNA synthesis in those cells compared with controls; cells with reduced proliferation, however, saw a 15 to 20 percent increase. This discrepancy suggests that atypical proliferation stems from changes in cell signaling.

Stem cells derived from blood cells of the children with idiopathic autisman intermediate step to generating precursor cellsproliferated typically, whereas those from boys with 16p11.2 deletions showed heightened proliferation. The scientists detailed their findings May 26 in Stem Cell Reports.

I am very excited about the idea of convergence between risk variants for psychiatric disordersin this case, idiopathic and 16p11.2, says Kristen Brennand, professor of psychiatry and genetics at Yale University, who did not take part in this research. Even if the direction and magnitude of effects are different, its intriguing that the same pathway is being hit.

The results mirror what is sometimes termed the Goldilocks effect in autism genetics, [in which] either increased or decreased dose or activity of the same gene can lead to risk of autism or another neurodevelopmental disorder, says Jeremy Veenstra-VanderWeele, professor of developmental neuropsychiatry at Columbia University, who was not involved in the study.

These findings suggest that this could be the case for neural precursor cell proliferation generally and perhaps also for response to basic FGF and even ERK signaling in some individuals, he says.

Most of the disruption in brain development in people with autism likely occurs prenatally but manifests during childhood, DiCicco-Bloom says. The results hint at a potential way to diagnose autism earlier in childhoodby taking blood cells, generating neural precursor cells and examining if they proliferate atypically. Then interventions might be employed earlier, DiCicco-Bloom says.

And investigating how autism alters the activity of enzymes such as P-ERK1 could lead to drugs or molecular tools to repair functional abnormalities, which might have an impact, though this is long into the future, DiCicco-Bloom says. Drugs that target P-ERK1 already exist, so clinical trials may one day test such drugs in autistic children who have known problems with this enzyme, he says.

Next, the researchers plan to study more children with idiopathic autism, as well as those with syndromic forms of the condition, such asfragile X syndrome,Rett syndrome andtuberous sclerosis complex, to see if problems with neural proliferation also occur in all these scenarios, DiCicco-Bloom says.

Other future experiments should include following these precursor cells longer to evaluate formation of more mature neurons, or even organoids, Veenstra-VanderWeele says.

Thisarticlewas originally published June 10 onSpectrum, the leading sitefor autism research news.

See more here:
Different Forms of Autism Have Opposite Problems with Brain Precursor Cells - The Scientist

Cell Biology

Published Peer Review History at PLOS: Observations from the past three years – The Official PLOS Blog – PLOS

Written by Lindsay Morton

Three years ago PLOS implemented our version of open peer review, which we named with our typical scrupulous precision and total disregard for word count: Published Peer Review History. Since then, the PLOS journals have together published over 18,000 articles with accompanying peer review history. Were pleased to share more preliminary observations based on our first three years of data below. But first, a bit of background

Open peer review can mean many different things. The main unifying feature is an element of openness somewhere in the peer review process, which can range from public comments on all submissions, to an open decision letter after acceptance. PLOS version of open peer review is simple, flexible and modular, dictated by the choices reviewers and authors make during the peer review and publication process.

All PLOS journals default to anonymous peer review. Reviewers have the option to sign their peer reviews if they wish to do so, and are advised of the potential for the review to be published. After an article has been accepted for publication, authors can opt-in to publish the Peer Review History, which includes the key documents from the peer review assessment:

The result is four possible gradations of openness in peer review.

It is very important, we think, to note that the benefits of Published Peer Review History are by no means predicated on reviewers signing their reviews. While reviewers have the opportunity to claim credit if they so choose, the value to the wider scholarly community stems from the availability of their comments. We want to make this absolutely clear because, too often, critique of open peer review can focus on signing, missing the more vital aspect of constructive feedback.

PLOS Peer Review History is organized, time stamped, and machine readable, with the goal of enabling future meta-research. Each element of the history package has a sub-DOI and is tagged and indexed, making it easy to discover and cite, even if youre not reading it on one of the PLOS journal websites. Its also included in AllofPLOS for easier mining and analysis.

You might be thinking so what? When PLOS introduced Peer Review History in 2019, various versions of public review had been available in the scholarly marketplace for a decade or moreat BMJ, EMBO Press, and eLife, just to name a few.

All implementations of open reviewsigned and unsigned, posted as public commentary or published after the factserve to improve transparency and accountability, to demonstrate the quality of peer review and reinforce the validity of the published research, to acknowledge and honor peer reviewers contributions to the literature, and to enrich the scientific record with more expertise.

Our own particular version emphasizes flexibility and author control. After acceptance, PLOS authors must click a check box and opt-in to have their peer reviews published. As a large international publisher with a very broad scope, our goal with Published Peer Review History, as with Open Science in general, has been to bring openness within easy reach for all, while at the same time respecting researchers different values and requirements across disciplines, career stages, and regions. Opt-in works at scale for all the researchers across our portfolio.

The opt-in model is somewhat unusual, as compared to the more established pioneers in Open Peer Review, many of whom mandate openness (e.g. BMJ) or use an opt-out model (e.g. EMBO Press). PLOS opt-in approach results in lower uptake: on average, 40% of PLOS authors opt-in, as compared to the reported greater than 95% of EMBO Press authors who dont opt-out. At the same time, PLOS large publication volume means that, even with a lower rate of uptake, the journals contribute significantly to the total number of articles with public peer reviews available across the published literature. (PLOS journals together published nearly 18,000 articles in 2020. For comparison, the same year eLife published 1,870 articles, BMJ Open published 3,610*, and the five EMBO Press journals published 1,063*.) This absolute scale is helpful with normalizing practices and behaviors.

The opt-in model, in combination with our size and breadth of scope also produces a wealth of data, which we hope can help us to better understand the communities we serve, and inform our future direction with regard to published review.

Since PLOS Published Peer Review History was first introduced, opt-in has remained a remarkably consistent 40%, year after year.**

PLOS two highly selective journals, PLOS Biology and PLOS Medicine, also saw the highest rates of Published Peer Review opt-in among accepted authors, followed by two of the four community journals, PLOS Computational Biology, and PLOS Genetics. PLOS ONE and the remaining two community journals, PLOS Pathogens and PLOS NTDs saw the lowest opt-in rates. PLOS ONEs broad scope and high publication volume accounts for its lower average opt-in rate. Lower adoption among Pathogens and NTDs authors as compared with the other community journals may likewise relate to subject-specific norms and preferences.

When PLOS ONE opt-in rates are broken out by discipline a pattern of subject-area preference becomes apparent. In fields with more than 100 published articles in the time period, opt-ins were strongest in computational biology, public health fields (womens health, public health, mental health), research on caregiving (healthcare, nursing), and specific medical disciplines (emergency medicine, neurology, obstetrics, urology, anesthesiology, pulmonology, clinical trials, etc.). Lower opt-in rates were observed in engineering, math, chemistry, materials science, earth science, geography and various branches of biology (molecular biology, microbiology, cell biology, biotechnology), as well as in fields where medical and bench science intersect, such as basic cancer research.

While clinical in their potential translational applications, PLOS NTDs and PLOS Pathogens frequently publish research on the molecular and cellular aspects of disease, and therefore might expect commensurately lower opt-in rates.

However, PLOS Biology also publishes in the biological fields where PLOS ONE opt-in tends to be weakeryet it has the highest opt-in rate of any journal. Why is that? Perhaps, the journals hands-on, personalized editorial and peer review process influences author opt-in. This would be a fascinating area for investigation.

PLOS has always allowed reviewers to sign their reviews if they choose, but it wasnt until the system updates introduced at the same time as Published Peer Review History (May 22, 2019) that we gained the ability to easily and systematically measure signing. Since then, weve received 49,555 signed reviews (17.81% of all completed reviews). Those signed reviews were performed by 40,276 individuals (about 19.26% of active reviewers) and were linked to 32,869 manuscripts (35.55% of manuscripts considered).

Overall, reviewers decisions to sign reviews are distributed across journals and subject areas in a pattern similar to authors decisions to publish reviews. Signing rates were higher in public health, medicine, and related disciplines and less common in some branches of biology, as well as the physical sciences, earth sciences, engineering and math. Of articles with published peer reviews, 44% also had at least one signed review.

The clearest determinant of signed review was the reviewers recommendation (although reviewer recommendations are visible only to Academic Editors and the journal office). Signing rates were highest among reviewers recommending accept or revise decisions. For that reason, rates of signing on published articles (42.19%) are higher than for manuscripts generally.

At PLOS we have formal and informal conversations with our stakeholders and community members; we gather feedback in person and by email; we conduct surveys and structured interviews; we do meta-research; we observe.

Three years ago, PLOS chose an opt-in over an opt-out model of published review for a number of reasons. Our in-house editorial teams and editorial boards alike were committed to open peer review, and committed to ensuring it was only received positively by giving authors a real choice in the decision. More practically, PLOS serves more than 200 communities of research, each with their own needs and priorities. Open peer review is too important a development to force on those who have concerns and need to see a community embrace it first. Therefore, we chose to make openness easy. By leaving the door open, hopefully we can learn more from those who choose to walk through. And, its our hope that information like this can help inform the next round of discussions, innovations, and policies, leading ultimately to a more efficient, equitable, and trustworthy peer review system.

*Data from Web of Science, May 14, 2022

**All data current through May 9, 2022 unless otherwise noted. To be eligible for inclusion articles must have been submitted after May 22, 2019. Published Peer Review History is available at all PLOS journals, including launched in 2021, however only data from the seven long-established journals is included here.

Read more from the original source:
Published Peer Review History at PLOS: Observations from the past three years - The Official PLOS Blog - PLOS

Cell Biology

Tessa Therapeutics to Host Scientific Session on CD30 CAR-T targeting of CD30+ Lymphomas at the SDCT-REMEDIS Cell Therapy Conference 2022 – Yahoo…

Tessa Therapeutics Ltd

SINGAPORE, June 13, 2022 (GLOBE NEWSWIRE) -- Tessa Therapeutics Ltd. (Tessa), a clinical-stage cell therapy company developing next-generation cancer treatments for hematological malignancies and solid tumors, today announced that the company will host a scientific session during the SDCT-REMEDIS Cell Therapy Conference 2022 being held virtually from June 23-24, 2022.

Tessas scientific session will focus on CD30 CAR-T targeting of CD30+ lymphomas and will feature a presentation from Dr. Ivan Horak, Chief Medical Officer and Chief Scientific Officer of Tessa Therapeutics. The discussion will be moderated by Dr. Han Chong Toh, Deputy Medical Director, National Cancer Centre Singapore (NCCS), Associate Professor, Cancer & Stem Cell Biology Program and SingHealth-Duke Global Health Institute, Duke-NUS, and Head of Cancer Immunotherapy at the SingHealth Duke-NUS Cell Therapy Centre.

Tessa is currently advancing two clinical programs leveraging distinct CD30 CAR-T technologies for the treatment of CD30+ lymphomas. Tessas lead clinical program TT11 is an autologous CD30 targeting CAR-T therapy currently being investigated as a potential treatment for relapsed or refractory classical Hodgkin lymphoma. Additionally, Tessa is developing an allogenic off-the-shelf CD30-CAR EBVST cell therapy TT11X targeting relapsed or refractory CD30-positive lymphomas. Data demonstrating the safety and efficacy of both programs was previously presented at the 2021 ASH Annual Meeting.

We are very pleased to host a scientific session at the SDCT-REMEDIS Cell Therapy Conference 2022 as it provides an opportunity to educate researchers on opportunities to treat CD30-positive lymphomas via CAR-T and the unique approaches being advanced by Tessa, said Dr. Horak. We look forward to progressing clinical programs investigating our autologous (TT11) and allogenic (TT11X) CAR-T technologies during 2022, with several development milestones expected throughout the year.

Story continues

Details on the scientific session are as follows:

Presentation Title:

CD30 CAR-T targeting of CD30+ Lymphomas

Moderator:

Dr. Han Chong Toh, Deputy Medical Director, National Cancer Centre Singapore (NCCS), Associate Professor, Cancer & Stem Cell Biology Program and SingHealth-Duke Global Health Institute, Duke-NUS, and Head of Cancer Immunotherapy at the SingHealth Duke-NUS Cell Therapy Centre

Presenter:

Dr. Ivan Horak, Chief Medical Officer and Chief Scientific Officer of Tessa Therapeutics

Date and Time:

June 23, 2022, 3:25 p.m. (SGT)/3:25 a.m. (EDT)

About Tessa Therapeutics

Tessa Therapeutics is a clinical-stage biotechnology company developing next-generation cell therapies for the treatment of hematological cancers and solid tumors. Tessas lead clinical asset, TT11, is an autologous CD30-CAR-T therapy currently being investigated as a potential treatment for relapsed or refractory classical Hodgkin lymphoma (Phase 2). TT11 has been granted RMAT designation by the FDA and PRIME designation by European Medicine Agency. Tessa is also advancing an allogeneic off-the shelf cell therapy platform targeting a broad range of cancers in which Epstein Barr Virus Specific T Cells (EBVSTs) are augmented with CD30-CAR. A therapy using this platform is currently the subject of a Phase 1 clinical trial in CD30-positive lymphomas. Tessa has its global headquarters in Singapore, where the company has built a state of the art, commercial cell therapy manufacturing facility. For more information on Tessa, visit http://www.tessacell.com.

Cautionary Note on Forward Looking Statements

This press release contains forward-looking statements (within the meaning of the Private Securities Litigation Reform Act of 1995, to the fullest extent applicable) including, without limitation, with respect to various regulatory filings or clinical study developments of the Company. You can identify these statements by the fact that they use words such as anticipate, estimate, expect, project, intend, plan, believe, target, may, assume or similar expressions. Any forward-looking statements in this press release are based on managements current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those related to the Companys financial results, the ability to raise capital, dependence on strategic partnerships and licensees, the applicability of patents and proprietary technology, the timing for completion of the clinical trials of its product candidates, whether and when, if at all, the Companys product candidates will receive marketing approval, and competition from other biopharmaceutical companies. The Company cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made, and disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent the Companys views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. The Companys products are expressly for investigational use pursuant to a relevant investigational device exemption granted by the U.S. Food & Drug Administration, or equivalent competent body.

Tessa Therapeutics Investor Contact

Wilson W. CheungChief Financial Officerwcheung@tessacell.com

Tessa Therapeutics Media Contact

Tiberend Strategic Advisors, Inc.Bill Borden+1-732-910-1620bborden@tiberend.com

Dave Schemelia+1-609-468-9325dschemelia@tiberend.com

View original post here:
Tessa Therapeutics to Host Scientific Session on CD30 CAR-T targeting of CD30+ Lymphomas at the SDCT-REMEDIS Cell Therapy Conference 2022 - Yahoo...

Cell Biology

Dren Bio Announces $65 Million Series B Financing to Advance its Lead Asset into the Clinic and to Accelerate Development of New Product Candidates…

FOSTER CITY, Calif.--(BUSINESS WIRE)--Dren Bio, Inc. (Dren Bio or the Company) today announced the completion of their $65 million Series B financing, pushing the Companys total capital received to date over $156 million. Following the financing, Dren Bio is well-capitalized to reach multiple key inflection points across both its drug discovery programs over the coming years.

We are truly grateful for all the support we continue to receive from such an outstanding syndicate of investors, said Nenad Tomasevic, Ph.D., Chief Executive Officer of Dren Bio. This financing comes at the perfect time as we prepare to initiate the first clinical trial evaluating DR-01, our lead asset, in patients with Large Granular Lymphocytic leukemia or cytotoxic lymphomas in mid-2022. In addition to advancing DR-01, the proceeds from this latest round will also enable us to further expand the development of our internal pipeline using our proprietary Targeted Myeloid Engager and Phagocytosis Platform.

The Series B financing was co-led by Aisling Capital and HBM Healthcare Investments, with participation by new marquee investors Pfizer, ArrowMark Partners and Revelation Partners. There was also significant participation in the round by Dren Bios existing insiders SR One, 8VC, Taiho Ventures, BVF Partners, Mission BioCapital and Alexandria Venture Investments, amongst others. In connection with the closing of the financing, the Company announced that Andrew Schiff, M.D., of Aisling Capital, and Chandra P. Leo, M.D., of HBM Partners, will join its Board of Directors.

We were thoroughly impressed by Dren Bios diversified R&D portfolio that encompasses two distinct therapeutic antibody programs including their attractive proprietary platform, said Dr. Schiff, Managing Partner at Aisling Capital. We are excited by the opportunity to support Dren Bio in progressing on their mission to deliver revolutionary therapies to patients with severe unmet needs, starting with difficult-to-treat cancers.

Dr. Leo, of HBM Partners, added, Over the last 18 months, Dren Bio has delivered robust preclinical data for their lead asset DR-01 and for their unique technology to induce myeloid cell engagement and phagocytosis. With this new financing, the Company is well positioned to rapidly advance DR-01 towards clinical proof-of-concept and to demonstrate the broad potential of their highly differentiated platform.

Proceeds from the financing will enable Dren Bio to continue advancement of its broad internal pipeline comprised of multiple development candidates approaching the clinic. The Companys lead asset, DR-01, is designed to precisely eliminate a subset of immune cells which are the underlying cause of certain hematologic malignancies and well-defined autoimmune disorders, both of which will be evaluated using its current funding. Dren Bios position as an emerging leader in the antibody therapeutics space is further strengthened by the exceptional prospects of its Targeted Myeloid Engager and Phagocytosis Platform. Bispecific antibodies generated using the proprietary platform have been shown to produce effects that are well-differentiated from other competing technologies including T cell engagers, antibody-dependent cellular cytotoxicity (ADCC) antibodies and antibody-drug conjugates. In addition to their profound and multi-pronged mechanism of action, initial development candidates have been very well tolerated in non-human primates, which should enable their utilization in both oncology and non-oncology indications. With its current funding, Dren Bio now has the opportunity to demonstrate the vast potential of its platform to produce therapies for a wide array of patients.

About Dren Bio

Dren Bio is a privately held, clinical-stage biopharmaceutical company focused on developing therapeutic antibodies for the treatment of cancer, autoimmune and other serious diseases. The Companys senior leadership team and scientific advisors have significant expertise covering the discovery and development of antibody-based product candidates designed to selectively target and deplete pathologic cells, protein aggregates and other disease-causing agents. Dren Bios pipeline encompasses two distinct programs, the first focusing on the engineering of antibodies with enhanced antibody-dependent cellular cytotoxicity (ADCC) capabilities and the second revolving around its proprietary Targeted Myeloid Engager and Phagocytosis Platform. For more information about Dren Bio and its two programs, please visit the Companys website at http://www.drenbio.com.

About Dren Bios Enhanced ADCC Program

Dren Bios Enhanced ADCC Program incorporates a validated and well understood technology for which the Companys senior leadership team has extensive experience. The lead product candidate from this program, DR-01, has been shown preclinically to induce rapid ADCC of a cell type that possesses intrinsic cytotoxic potential and is the primary driver of disease in several rare, hematologic malignancies. In addition to these initial cancers, DR-01 is also being evaluated for potential use in treating a number of other indications, including various autoimmune disorders for which the same cytotoxic immune cells are known to play a key role.

About Dren Bios Targeted Myeloid Engager and Phagocytosis Platform

The Companys Targeted Myeloid Engager and Phagocytosis Platform is an innovative and scientifically compelling approach towards discovering bispecific antibodies for the co-engagement of a conserved, microbial phagocytic receptor highly expressed on myeloid cells, along with a specific target antigen expressed on a pathologic cell or other disease-causing agent of interest. The unique biology of the novel phagocytic receptor enables controlled myeloid cell activation only in the presence of the desired target antigen, thereby resulting in localized cytokine release for an increased therapeutic index and more favorable safety profile. Bispecific antibodies from the platform that are being developed for the treatment of cancer elicit a powerful, multi-pronged mechanism of action that encompasses (i) direct coupling of myeloid cells with cancer cells, (ii) stimulation of myeloid cells for the release of key cytokines known to reprogram tumor associated macrophages and reset the immunosuppressive tumor microenvironment, (iii) phagocytosis and killing of tumor cells, and (iv) presentation of tumor neoantigens for activating effector and memory T cell responses necessary to achieve anti-tumor immunity. The significant upregulation of Antigen Presenting Machinery (APM) signature genes and boost to both the number and diversity of peptides presented, collectively support the potential of future drug candidates discovered using the platform to provide longer-lasting responses than those currently observed by other comparable immune cell engaging technologies.

Dren Bios first development candidate using the platform, DR-0201, co-engages a validated target expressed on the surface of B cells. Exciting preclinical data generated to date from both functional assays and in vivo animal models consistently demonstrate the ability of DR-0201 to induce robust B cell depletion using a differentiated approach when compared head-to-head against ADCC antibody and T cell engager technologies. DR-0201 also consistently exhibits an attractive safety profile, which has now been observed in multiple studies of non-human primates. In addition to Dren Bios initial efforts focused on difficult-to-treat cancers, DR-0201 is being evaluated in autoimmune disorders for which the depletion of B cells has previously been validated in patients. Beyond DR-0201, the Companys early-stage pipeline also includes the discovery of bispecific antibodies against well-known solid tumor targets as well as exciting new development opportunities to potentially treat severe, life-threatening non-oncology indications such as light chain (AL) amyloidosis, transthyretin (ATTR) amyloidosis, and Alzheimers disease, through the removal of harmful protein aggregates.

Source: Dren Bio, Inc.

Read more from the original source:
Dren Bio Announces $65 Million Series B Financing to Advance its Lead Asset into the Clinic and to Accelerate Development of New Product Candidates...

Cell Biology

New Comprehensive Map Ties Every Human Gene to Its Function – SciTechDaily

Data for a new gene-function map are available for other scientists to use. Its a big resource in the way the human genome is a big resource, in that you can go in and do discovery-based research, says Professor Jonathan Weissman.

Scientists used their single-cell sequencing tool Perturb-seq on every expressed gene in the human genome, linking each to its job in the cell.

Genetics research has advanced rapidly over the last few decades. For example, just a few months ago scientists announced the first complete, gap-free human genome sequencing. Now researchers have advanced again, creating the first comprehensive functional map of genes that are expressed in human cells.

The Human Genome Project was an ambitious initiative to sequence every piece of human DNA. The project drew together collaborators from research institutions around the world, including MITs Whitehead Institute for Biomedical Research, and was finally completed in 2003. Now, over two decades later, MIT Professor Jonathan Weissman and colleagues have gone beyond the sequence to present the first comprehensive functional map of genes that are expressed in human cells. The data from this project, published online on June 9, 2022, in the journal Cell, ties each gene to its job in the cell, and is the culmination of years of collaboration on the single-cell sequencing method Perturb-seq.

The data are available for other scientists to use. Its a big resource in the way the human genome is a big resource, in that you can go in and do discovery-based research, says Weissman, who is also a member of the Whitehead Institute and an investigator with the Howard Hughes Medical Institute. Rather than defining ahead of time what biology youre going to be looking at, you have this map of the genotype-phenotype relationships and you can go in and screen the database without having to do any experiments.

CRISPR, which stands for clustered regularly-interspaced short palindromic repeats, a genome editing tool invented in 2009 made it easier than ever to edit DNA. It is easier, faster, less expensive, and more accurate than previous genetic editing methods.

The screen allowed the researchers to delve into diverse biological questions. They used it to explore the cellular effects of genes with unknown functions, to investigate the response of mitochondria to stress, and to screen for genes that cause chromosomes to be lost or gained, a phenotype that has proved difficult to study in the past. I think this dataset is going to enable all sorts of analyses that we havent even thought up yet by people who come from other parts of biology, and suddenly they just have this available to draw on, says former Weissman Lab postdoc Tom Norman, a co-senior author of the paper.

Pioneering Perturb-seq

The project takes advantage of the Perturb-seq approach that makes it possible to follow the impact of turning on or off genes with unprecedented depth. This method was first published in 2016 by a group of researchers including Weissman and fellow MIT professor Aviv Regev, but could only be used on small sets of genes and at great expense.

The massive Perturb-seq map was made possible by foundational work from Joseph Replogle, an MD-PhD student in Weissmans lab and co-first author of the present paper. Replogle, in collaboration with Norman, who now leads a lab at Memorial Sloan Kettering Cancer Center; Britt Adamson, an assistant professor in the Department of Molecular Biology at Princeton University; and a group at 10x Genomics, set out to create a new version of Perturb-seq that could be scaled up. The researchers published a proof-of-concept paper in Nature Biotechnology in 2020.

The Perturb-seq method uses CRISPR-Cas9 genome editing to introduce genetic changes into cells, and then uses single-cell RNA sequencing to capture information about the RNAs that are expressed resulting from a given genetic change. Because RNAs control all aspects of how cells behave, this method can help decode the many cellular effects of genetic changes.

Since their initial proof-of-concept paper, Weissman, Regev, and others have used this sequencing method on smaller scales. For example, the researchers used Perturb-seq in 2021 to explore how human and viral genes interact over the course of an infection with HCMV, a common herpesvirus.

In the new study, Replogle and collaborators including Reuben Saunders, a graduate student in Weissmans lab and co-first author of the paper, scaled up the method to the entire genome. Using human blood cancer cell lines as well noncancerous cells derived from the retina, he performed Perturb-seq across more than 2.5 million cells, and used the data to build a comprehensive map tying genotypes to phenotypes.

Delving into the data

Upon completing the screen, the researchers decided to put their new dataset to use and examine a few biological questions. The advantage of Perturb-seq is it lets you get a big dataset in an unbiased way, says Tom Norman. No one knows entirely what the limits are of what you can get out of that kind of dataset. Now, the question is, what do you actually do with it?

The first, most obvious application was to look into genes with unknown functions. Because the screen also read out phenotypes of many known genes, the researchers could use the data to compare unknown genes to known ones and look for similar transcriptional outcomes, which could suggest the gene products worked together as part of a larger complex.

The mutation of one gene called C7orf26 in particular stood out. Researchers noticed that genes whose removal led to a similar phenotype were part of a protein complex called Integrator that played a role in creating small nuclear RNAs. The Integrator complex is made up of many smaller subunits previous studies had suggested 14 individual proteins and the researchers were able to confirm that C7orf26 made up a 15th component of the complex.

They also discovered that the 15 subunits worked together in smaller modules to perform specific functions within the Integrator complex. Absent this thousand-foot-high view of the situation, it was not so clear that these different modules were so functionally distinct, says Saunders.

Another perk of Perturb-seq is that because the assay focuses on single cells, the researchers could use the data to look at more complex phenotypes that become muddied when they are studied together with data from other cells. We often take all the cells where gene X is knocked down and average them together to look at how they changed, Weissman says. But sometimes when you knock down a gene, different cells that are losing that same gene behave differently, and that behavior may be missed by the average.

The researchers found that a subset of genes whose removal led to different outcomes from cell to cell were responsible for chromosome segregation. Their removal was causing cells to lose a chromosome or pick up an extra one, a condition known as aneuploidy. You couldnt predict what the transcriptional response to losing this gene was because it depended on the secondary effect of what chromosome you gained or lost, Weissman says. We realized we could then turn this around and create this composite phenotype looking for signatures of chromosomes being gained and lost. In this way, weve done the first genome-wide screen for factors that are required for the correct segregation of DNA.

I think the aneuploidy study is the most interesting application of this data so far, Norman says. It captures a phenotype that you can only get using a single-cell readout. You cant go after it any other way.

The researchers also used their dataset to study how mitochondria responded to stress. Mitochondria, which evolved from free-living bacteria, carry 13 genes in their genomes. Within the nuclear DNA, around 1,000 genes are somehow related to mitochondrial function. People have been interested for a long time in how nuclear and mitochondrial DNA are coordinated and regulated in different cellular conditions, especially when a cell is stressed, Replogle says.

The researchers found that when they perturbed different mitochondria-related genes, the nuclear genome responded similarly to many different genetic changes. However, the mitochondrial genome responses were much more variable.

Theres still an open question of why mitochondria still have their own DNA, said Replogle. A big-picture takeaway from our work is that one benefit of having a separate mitochondrial genome might be having localized or very specific genetic regulation in response to different stressors.

If you have one mitochondria thats broken, and another one that is broken in a different way, those mitochondria could be responding differentially, Weissman says.

In the future, the researchers hope to use Perturb-seq on different types of cells besides the cancer cell line they started in. They also hope to continue to explore their map of gene functions, and hope others will do the same. This really is the culmination of many years of work by the authors and other collaborators, and Im really pleased to see it continue to succeed and expand, says Norman.

Reference: Mapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq by Joseph M. Replogle, Reuben A. Saunders, Angela N. Pogson, Jeffrey A. Hussmann, Alexander Lenail, Alina Guna, Lauren Mascibroda, Eric J. Wagner, Karen Adelman, Gila Lithwick-Yanai, Nika Iremadze, Florian Oberstrass, Doron Lipson, Jessica L. Bonnar, Marco Jost, Thomas M. Norman and Jonathan S. Weissman, 9 June 2022, Cell.DOI: 10.1016/j.cell.2022.05.013

See the article here:
New Comprehensive Map Ties Every Human Gene to Its Function - SciTechDaily

Cell Biology

SG$25 million grant awarded to multi-institution research team working to improve liver cancer outcomes – EurekAlert

Singapore, 13 June 2022 A multidisciplinary team of clinician-scientists and researchers has been awarded a SG$25 million grant to conduct clinical and translational studies and cutting-edge patient-data analysis that will lead to improvements in clinical practice and better health outcomes for patients with the primary liver cancer, hepatocellular carcinoma (HCC). Led by the National Cancer Centre Singapore (NCCS) in collaboration with A*STARs Genome Institute of Singapore (GIS) and Institute of Molecular and Cell Biology (IMCB), the Cancer Science Institute of Singapore, at the National University of Singapore, and Duke-NUS Medical School, the PLANet 2.0 (Precision Medicine in Liver Cancer across an Asia-Pacific Network) research programme is supported by the National Research Foundation Singapore under its Open Fund-Large Collaborative Grant (OFLCG21Jun-0016) which is administered by the Singapore Ministry of Healths National Medical Research Council (NMRC).

Liver cancer is the sixth most common cancer in the world and fourth most common cause of cancer deaths globally.[1] In Singapore, it is the third most common cause of cancer deaths in males and fifth most common cause in females[2]; as HCC is usually diagnosed at a late stage, when prognosis is poor. In addition, current standard therapies for HCC, including systemic therapies, have poorer efficacy compared to systemic treatment for other common cancers. This is largely because there are currently no validated biomarkers to guide clinicians in the choice of the best therapy for an individual patient with HCC.

PLANet 2.0 builds on the success of our earlier programme, PLANet 1.0, bringing together leading clinical and translational research experts across Singapore to address the urgent, unmet clinical need for more targeted and efficient treatment for liver cancer so that patients may have better outcomes, said Professor Pierce Chow, Principal Investigator of the study and Senior Consultant, Department of Hepato-Pancreato-Biliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and NCCS.

Laying the foundation for PLANet 2.0

The PLANet 2.0 research team first came together in 2016 for PLANet 1.0, a five-year multidisciplinary research programme to better understand the tumour biology and mechanisms of HCC. Detailed understanding of the landscape of HCC and robust predictive biomarkers is key to improving clinical outcomes in HCC. Current clinical practice and treatment recommendations for HCC are hindered by the absence of biomarkers that can guide therapy and therefore depend on the individual clinicians judgement, experience and preference.

While immunotherapy is currently the most effective systemic therapy for HCC, only a subset of patients responds to it, with 30% being the best overall response rate. PLANet 1.0 found that HCCs molecular landscape is extremely heterogeneous and shed light on novel mechanisms underpinning the disease, including how it reverts to foetal forms to escape the bodys immunological defence, highlighting why HCC is difficult to treat.[3]

Conducting PLANet 2.0 in Singapore and the region

PLANet 2.0 will conduct two clinical studies that will serve as proof-of-concept for PLANet 1.0s translational findings and allow the team to uncover predictive biomarkers. In the first clinical study, a minimum of 30 patients with HCC who have undergone liver resection or surgery for the tumour will receive immunotherapy after surgery to reduce the chance of the tumour coming back. The second clinical study is a randomised controlled trial for patients with intermediate to advanced HCC ineligible for surgery. These surgically unresectable patients will be treated with Selective Internal Radiation Therapy (SIRT) with yttrium-90 followed by immunotherapy in a novel radiotherapy and immunotherapy combination. This study will enrol 176 patients. The two clinical studies will run concurrently and the recruitment and administration of the clinical studies will be in multiple sites in Singapore (Changi General Hospital, National Cancer Centre Singapore, National University Cancer Institute, Singapore, National University Hospital, Sengkang General Hospital, Singapore General Hospital and Tan Tock Seng Hospital) and 11 other hospitals in the Asia-Pacific region.

These studies leverage their longitudinal study designs to obtain before and after treatment patient samples and clinical data and aim to identify and validate biomarkers that correlate with clinical outcomes including response and resistance to therapy. The research teams will use a wide spectrum of investigations leveraging on their multidisciplinary expertise in the fields of epigenomics, genomics, immunomics, metabolomics, proteomics, data science and clinical care to better understand the landscape of the HCC tumour micro-environment and biomarker co-localisation. This convergence of approaches will enable robust validation of conclusions and inform the change needed in clinical practice to institute more efficacious and personalised treatment for HCC patients in the future.

Dr Tam Wai Leong, Associate Director and Group Leader of the Laboratory of Translational Cancer Biology at GIS, as well as Theme PI, said, GIS is excited to be part of this multi-disciplinary and multi-institutional study aimed at improving clinical outcomes for liver cancer patients. The project will harness the power of genomic technologies to unlock the secrets of disease genes through deep profiling of consented clinical trial biosamples. The longitudinal tracking of tumours from the same patients will reveal critical genetic insights on why some cancer patients fare better than others, ultimately aiding in tailoring better treatment strategies for patients.

Professor Vinay Tergaonkar, Research Director at IMCB and Theme PI, said, Although the composition of various types of cells that constitute a tumour are well-studied in many cancers including HCC, this study would be one of the first ever, wherein changes in the physical co-localisation of various cell populations of the HCC microenvironment will be deciphered during the course of therapy. This information will be beneficial in guiding future therapeutic development.

The Open Fund-Large Collaborative Grant (OF-LCG) Programme

The annual OF-LCG grant call supports the efforts of the best research teams in Singapore to conduct patient-centric translationalresearch with the goal of advancing human health and wellness and creating economic value. Cancer is one of the seven areas identified as national priorities for research in Singapore.

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

About the National Cancer Centre of Singapore

The National Cancer Centre Singapore (NCCS) is a leading national and regional tertiary cancer centre with specialists who are experts in treating cancer. NCCS attends to the majority of cancer cases in Singapores public healthcare sector. In addition to offering holistic and multidisciplinary oncology care, our clinicians and scientists collaborate with local and international partners to conduct robust, cutting-edge clinical and translational research. To achieve the vision of being a global leading cancer centre, NCCS offers world class care and shares its depth of experience and expertise by training local and overseas medical professionals.

To meet growing needs, the new NCCS building will be completed in 2022 with increased capacity and expanded facilities dedicated to cancer care, rehabilitation, research and education. To give patients the best treatment outcomes, NCCS will offer access to advanced and innovative treatment such as proton therapy at the new Goh Cheng Liang Proton Therapy Centre.

For more information, please visit: http://www.nccs.com.sg

About the Agency for Science, Technology and Research (A*STAR)

A*STAR is Singapore's lead public sector R&D agency. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit the economy and society. As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by improving societal outcomes in healthcare, urban living, and sustainability. A*STAR plays a key role in nurturing scientific talent and leaders for the wider research community and industry. A*STARs R&D activities span biomedical sciences to physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit http://www.a-star.edu.sg.

Follow us on

Facebook | LinkedIn | Instagram | YouTube

About A*STARs Genome Institute of Singapore (GIS)

The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to achieve extraordinary improvements in human health and public prosperity. Established in 2000 as a centre for genomic discovery, the GIS pursues the integration of technology, genetics and biology towards academic, economic and societal impact, with a mission to "read, reveal and write DNA for a better Singapore and world".

Key research areas at the GIS include Precision Medicine & Population Genomics, Genome Informatics, Spatial & Single Cell Systems, Epigenetic & Epitranscriptomic Regulation, Genome Architecture & Design, and Sequencing Platforms. The genomics infrastructure at the GIS is also utilised to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

For more information about GIS, please visit http://www.a-star.edu.sg/gis.

About A*STARs Institute of Molecular and Cell Biology (IMCB)

The vision of Institute of Molecular and Cell Biology (IMCB) is to be a premier cell and molecular biology institute which addresses the mechanistic basis of human diseases and its mission is to conduct cutting-edge discovery research in disease pathways; to groom early career researchers to be future leaders in research; and to collaborate with the public sector, medical and industry communities for research impact. IMCB plays an important role training and recruiting scientific talents, and has contributed to the development of other research entities in Singapore. Its success in fostering a biomedical research culture in Singapore has catalysed Singapores transformation into an international hub for biomedical research, development and innovation.

Funded by A*STAR, IMCBs use-inspired research comprises 4 major programmes: Neurometabolism in Health and Diseases; Cancer Signalling and Therapies; Cell Biology and Therapies; and Innovative Technologies IMCBs technologies and platforms focus on Mouse Models of Diseases, Molecular Histopathology, Cellular Microscopy, and Proteomics & Metabolomics. For more information about IMCB, please visit http://www.a-star.edu.sg/imcb.

About the Cancer Science Institute of Singapore (CSI Singapore)

The Cancer Science Institute of Singapore (CSI) is one of only six Research Centres of Excellence established by the Government of Singapore with funding from the National Research Foundation and the Ministry of Education. Its mission is to better understand the causes of human cancer across Asia, and thereby improve its detection, treatment and prevention for the benefit of the patients. The CSIs outstanding researchers and excellent scientific facilities create an energetic environment for ground-breaking research and world-class training. The CSI is internationally recognized for its innovative research on the biology of cancers prevalent in Asia, and for taking new methods for cancer treatment from the laboratory to the clinic. Through its local and global partnerships,the CSI works with leading minds from multiple scientific and clinical disciplines in Singapore, the USA and Europe, both in academia and in industry. For more information on CSI Singapore, visit https://www.csi.nus.edu.sg/web/

About Duke-NUS Medical School

Duke-NUS is Singapores flagship graduate entry medical school, established in 2005 with a strategic, government-led partnership between two world-class institutions: Duke University School of Medicine and the National University of Singapore (NUS). Through an innovative curriculum, students at Duke-NUS are nurtured to become multi-faceted Clinicians Plus poised to steer the healthcare and biomedical ecosystem in Singapore and beyond. A leader in ground-breaking research and translational innovation, Duke-NUS has gained international renown through its five signature research programmes and 10 centres. The enduring impact of its discoveries is amplified by its successful Academic Medicine partnership with Singapore Health Services (SingHealth), Singapores largest healthcare group. This strategic alliance has spawned 15 Academic Clinical Programmes, which harness multi-disciplinary research and education to transform medicine and improve lives.

For more information, please visit http://www.duke-nus.edu.sg

For more information, please contact:

National Cancer Centre Singapore

Dharshini Subbiah

Assistant Manager, Corporate Communications

Mobile : 9616 7532

Email : dharshini.subbiah@nccs.com.sg

Agency for Science, Technology and Research (A*STAR)

Sharmaine Loh

Assistant Head, Corporate Communications

Mobile: 98621834

Email: sharmaine_loh@hq.a-star.edu.sg

[1] Singal, A. G., Lampertico, P. & Nahon, P. Epidemiology and surveillance for hepatocellular carcinoma: New trends. J. Hepatol. 72, 250261 (2020)

[2] National Registry of Diseases Office. (2022, Jan).Singapore Cancer Registry Annual Report 2019.

[3] Zhai, W. et al. Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study. Natl. Sci. Rev. (2021) doi:10.1093/nsr/nwab192

More here:
SG$25 million grant awarded to multi-institution research team working to improve liver cancer outcomes - EurekAlert

Cell Biology

Postdoctoral Researcher / Doctoral Researcher in the Functional Cancer Genomics Group job with UNIVERSITY OF HELSINKI | 297116 – Times Higher…

The Functional Cancer Genomics group led by Dr. Sakari Vanharanta at the Translational Cancer Medicine Program, Faculty of Medicine, University of Helsinki, Finland, invites applications for the position of

POSTDOCTORAL RESEARCHER / DOCTORAL RESEARCHER

The goal of our research is to understand how cancers develop and spread, and how this knowledge could be used for the development of new approaches for therapy. We study how cancer mutations activate oncogenic programs and how these programs lead to cancer progression and metastasis. Specifically, our aims are to understand (i) how normal transcriptional programs are co-opted for carcinogenesis, (ii) how these programs interact with genetically activated oncogenic pathways, (iii) what the critical pro-tumorigenic mechanisms of cancer mutations are, and (iv) whether cancer-specific cellular programs lead to molecular vulnerabilities that could be exploited for cancer therapy and patient benefit. Our research combines experimental cancer models and human cancer data sets with state-of-the-art genomics (e.g. chromatin and transcriptional profiling), mechanistic analysis using various methods of genetic perturbation, and unbiased functional genetic screens (e.g. CRISPR/Cas9 screens), as demonstrated by our recent work (Patel et al. Nature 2022).

The Functional Cancer Genomics group consists of biomedical scientists with diverse backgrounds and expertise. We have strong international connections and work in a collaborative manner towards shared goals. After eight years at the University of Cambridge, the team has recently moved to Helsinki, and is located at Biomedicum Helsinki within the Academic Medical Center Helsinki, which provides a multidisciplinary research environment for basic and translational research with state-of-the-art facilities, cutting-edge technologies and synergistic expertise of several research groups.

We are looking for highly motivated biomedical scientists with a strong background in molecular and cell biology, biochemistry, functional genomics, cancer biology, genetics, computational biology, bioinformatics, or other related disciplines. At the postdoctoral level a successful candidate should have a PhD degree in an appropriate biological subject and a demonstrated track record of peer-reviewed publications. At the pre-doctoral level, previous experience in biomedical research or bioinformatics is considered an advantage.

Candidates should be able to demonstrate abstract thinking as well as potential to develop and pursue scientific projects in the field of cancer biology. Excellent communication skills in English and organizational abilities are expected. The position is available as soon as the selected candidates are available. The project allows initially a three-year fixed-term position. Salary will be commensurate with qualifications and experience based on the University guidelines.

Please submit your application as a single PDF file through the Universitys electronic recruitment system. If you need technical support with the recruitment system, please contact recruitment@helsinki.fi.

The deadline for applications is 25 July 2022.

Please attach the following documents to your application as a single PDF file:

For more information on the positions and specific projects, please contact Dr. Sakari Vanharanta, sakari.vanharanta@helsinki.fi.

More information on the Translational Cancer Medicine Program can be found here.

For additional information about the application process, please contact the HR team at hr-ltdk@helsinki.fi.

Relevant publications:

Patel et al. The renal lineage factor PAX8 controls oncogenic signalling in kidney cancer. Nature (2022). https://doi.org/10.1038/s41586-022-04809-8Patel et al. Genomic control of metastasis. Br J Cancer. (2021) Jan;124(1):3-12.Rodrigues et al. NF-kappaB-dependent lymphoid enhancer co-option promotes renal carcinoma metastasis. Cancer Discov. (2018), Jul;8(7):850-865

Follow this link:
Postdoctoral Researcher / Doctoral Researcher in the Functional Cancer Genomics Group job with UNIVERSITY OF HELSINKI | 297116 - Times Higher...

Cell Biology

OSU researchers study quorum sensing in a gram-negative bacterium that displays social behaviors – News-Medical.Net

Oregon State University scientists have identified proteins that prevent a bacterial cell from becoming misguided by its own messaging, allowing it to instead wait for collective communication from its group.

The research is important because understanding this type of signaling, known as quorum sensing and integral to bacterial pathogens, opens the door to potential new drugs that can disrupt it and thwart infection.

Findings were published today in the Proceedings of the National Academy of Sciences.

Martin Schuster, a professor in OSU's Department of Microbiology in the colleges of Science and Agricultural Sciences, and doctoral student Parker Smith study quorum sensing in the pathogen Pseudomonas aeruginosa, a gram-negative bacterium that displays a variety of social behaviors.

P. aeruginosa, a common cause of lung and wound infections among hospital patients and people with weakened immune systems, is a model organism for quorum sensing research with a well understood signaling circuit, the scientists said.

"Sometimes single-celled organisms need to work together with other cells," Schuster said. "Bacteria and other single-celled microbes can coordinate behaviors and act as a group via quorum sensing, in which cells produce and sense a small chemical signal that is shared within the population."

As the signal is released from cells and reaches a high enough concentration in their environment, a quorum is achieved certain genes are simultaneously activated and specific group behaviors are set in motion, Smith said.

It's a strength-in-numbers approach that allows bacteria to join forces to do things they could not do by themselves, like causing infection in animals and plants, acquiring certain nutrients and competing against other microbes.

"Bacterial infection often involves toxins that only harm the host at high levels, when produced by all bacterial cells at once," Smith said.

A major unresolved question about quorum sensing, the researchers said, has been why the signal that's produced inside an individual cell is not sensed by that same cell before it is released, spurring the cell into premature, solo action.

"In essence, what prevents signal 'short-circuiting' from happening?" Schuster said. "Our research addresses this question that's fundamental to our understanding of quorum sensing."

Smith and Schuster learned that a set of proteins called antiactivators are crucial for short-circuit prevention. The proteins work as a quorum sensing "tuner" by causing cells to be less sensitive to the quorum signal.

The researchers developed bacterial strains that lacked two different types of antiactivator proteins and then looked at quorum sensing behaviors in individual cells.

"We found that without antiactivators, a fraction of cells in a P. aeruginosa population engaged in 'self-talk,'" Smith said. "In these cells, signal short-circuiting had activated quorum-sensing-dependent behaviors at all times, irrespective of cell density and without any communication with other cells. Our research shows how bacteria put the brakes on quorum sensing to achieve true communication in a group."

In addition to helping the quest for new antibiotics that can inhibit quorum sensing in bacterial pathogens, the findings also provide background knowledge useful for the engineering of cells with new properties in a field called synthetic biology, Schuster said.

The study was funded by the National Science Foundation.

Go here to read the rest:
OSU researchers study quorum sensing in a gram-negative bacterium that displays social behaviors - News-Medical.Net

Cell Biology

3D Cell Culture Market by Type, Application, End-user and Region – Global Forecast to 2027 – GlobeNewswire

Dublin, June 08, 2022 (GLOBE NEWSWIRE) -- The "3D Cell Culture Market by Type (Hydrogel, ECM, Hanging Drop, Bioreactor, Microfluidics, Magnetic Levitation), Application (Cancer, Stem Cell, Toxicology, Tissue Engineering), End User (Pharma, Biotech, Research, Cosmetics), Region - Global Forecast to 2027" report has been added to ResearchAndMarkets.com's offering.

The global 3D cell culture market is valued at an estimated USD 1.3 billion in 2022 and is projected to reach USD 2.6 billion by 2027, at a CAGR of 15.6% during the forecast period.

The growth of this market is mainly driven by factors such as the increasing focus on developing alternative methods to animal testing, growing focus on personalized medicine, increasing incidence of chronic diseases, and the availability of funding for research. On the other hand, a lack of infrastructure for 3D cell-based research and the high cost of cell biology research are expected to restrain the growth of this market during the forecast period.

The scaffold-based 3D cell culture segment accounted for the highest growth rate in the 3D Cell culture market, by type, during the forecast period

In 2021, the scaffold-based 3D cell culture segment accounted for the highest growth rate. The advantages of scaffolds in 3D cell culture, such as structural rigidity, the availability of attachment points, and support, have greatly driven the preference for scaffold-based 3D cell cultures and ensured the large share of this segment.

Asia Pacific: The fastest-growing region in the 3D Cell culture market

The Asia Pacific market is estimated to record the highest CAGR during the forecast period. This is attributed to the presence of favorable regulatory guidelines, government support for cell culture-based vaccine production, low manufacturing costs, and the growing focus of global market players on emerging Asian countries.

Key Topics Covered:

1 Introduction

2 Research Methodology

3 Executive Summary

4 Premium Insights4.1 3D Cell Culture Market Overview4.2 North America: 3D Cell Culture Market, by Type and Country (2021)4.3 3D Cell Culture Market Share, by Application, 2022 Vs. 20274.4 3D Cell Culture Market Share, by End-user, 2021 (USD Million)4.5 3D Cell Culture Market: Geographic Growth Opportunities

5 Market Overview5.1 Introduction5.2 Market Dynamics5.2.1 Drivers5.2.1.1 Increasing Focus on Developing Alternatives to Animal Testing5.2.1.2 Growing Focus on Personalized Medicine5.2.1.3 Increasing Incidence of Chronic Diseases5.2.1.4 Availability of Funding for Research5.2.1.5 Growing Demand for 3D Cell Culture5.2.2 Restraints5.2.2.1 Lack of Infrastructure for 3D Cell-Based Research5.2.2.2 High Cost of Cell Biology Research5.2.3 Opportunities5.2.3.1 Emergence of Microfluidics-Based 3D Cell Culture5.2.3.2 Emerging Economies5.2.3.3 Regenerative Medicine as An Alternative to Organ Transplantation5.2.3.4 Risk of Pandemics and Communicable Diseases5.2.4 Challenges5.2.4.1 Lack of Consistency in 3D Cell Culture Products5.2.4.2 Plastic Waste Disposal5.3 Ranges/Scenarios5.4 Impact of the COVID-19 Outbreak on the 3D Cell Culture Market5.5 Pricing Analysis5.6 Technology Analysis5.7 Patent Analysis5.8 Value Chain Analysis5.9 Supply Chain Analysis5.10 Ecosystem Analysis of the 3D Cell Culture Market5.11 Key Conferences & Events in 2022-20235.12 Regulatory Analysis5.12.1 Regulatory Bodies, Government Agencies, and Other Organizations5.13 Porter's Five Forces Analysis5.14 Key Stakeholders and Buying Criteria

6 3D Cell Culture Market, by Type6.1 Introduction6.2 Scaffold-Based 3D Cell Cultures6.2.1 Hydrogels/Ecm Analogs6.2.1.1 Hydrogels/Ecm Analogs Dominate the Scaffold-Based 3D Cell Cultures Market6.2.2 Solid Scaffolds6.2.2.1 Solid Scaffolds Are Widely Adopted in Regenerative Medicine and Preclinical in Vitro Testing6.2.3 Micropatterned Surfaces6.2.3.1 Micropatterned Surfaces Enhance the Expression of Enzymes Levels and Drug Reactivity6.3 Scaffold-Free 3D Cell Cultures6.3.1 Low Attachment Plates6.3.1.1 Low Attachment Plates Are Expected to Grow at the Highest Rate in the Scaffold-Free 3D Cell Cultures Market6.3.2 Hanging Drop Plates6.3.2.1 Hanging Drop Plates Are Widely Used in Stem Cell Differentiation and Cytotoxicity Research6.3.3 3D Bioreactors6.3.3.1 3D Bioreactors Are Commonly Used in the Mass Production of Cells6.3.4 3D Petri Dishes6.3.4.1 Europe Will Witness the Highest Growth in the 3D Petri Dishes Market6.4 Microfluidics-Based 3D Cell Cultures6.4.1 Microfluidics-Based 3D Cell Cultures Will Grow at the Highest Rate in the 3D Cell Culture Market6.5 Magnetic & Bioprinted 3D Cell Cultures6.5.1 3D Cell Culture Can be Formed Without Media in Magnetic Levitation

7 3D Cell Culture Market, by Application7.1 Introduction7.2 Cancer & Stem Cell Research7.2.1 Rising Prevalence of Cancer is a Key Factor Driving the Growth of this Segment7.3 Drug Discovery & Toxicology Testing7.3.1 Increasing Adoption of Personalized Medicines to Support Market Growth7.4 Tissue Engineering & Regenerative Medicine7.4.1 Increasing Tissue Engineering & Regenerative Medicine Research to Drive this Market

8 3D Cell Culture Market, by End-user8.1 Introduction8.2 Pharmaceutical & Biotechnology Companies8.2.1 Pharmaceutical & Biotechnology Companies Are the Largest End-users of 3D Cell Culture Products8.3 Research Institutes8.3.1 Increasing Government Funding for Research & High Prevalence of Cancer Are Driving Market Growth8.4 Cosmetics Industry8.4.1 Focus on Developing Alternatives to Animal Testing is a Key Factor Driving Market Growth8.5 Other End-users

9 3D Cell Culture Market, by Region

10 Competitive Landscape10.1 Overview10.2 Key Player Strategies/Right to Win10.3 Market Share Analysis10.4 Revenue Share Analysis of the Top Market Players10.5 Company Evaluation Quadrant10.5.1 Stars10.5.2 Emerging Leaders10.5.3 Pervasive Players10.5.4 Participants10.6 Company Evaluation Quadrant: Start-Ups/Smes10.6.1 Progressive Companies10.6.2 Starting Blocks10.6.3 Responsive Companies10.6.4 Dynamic Companies10.7 Company Footprint Analysis10.7.1 Company Product Footprint10.7.2 Company Regional Footprint10.7.3 Competitive Benchmarking of Startup/Sme Players10.8 Competitive Scenario

11 Company Profiles11.1 Key Players11.1.1 Thermo Fisher Scientific, Inc.11.1.2 Merck Kgaa11.1.3 Corning Incorporated11.1.4 Lonza Group Ag11.1.5 Tecan Trading Ag11.1.6 Avantor, Inc.11.1.7 Reprocell Inc.11.1.8 3D Biotek LLC11.1.9 Emulate, Inc.11.1.10 Cn Bio Innovations Limited11.1.11 Synthecon, Incorporated11.1.12 Insphero Ag11.1.13 Kirkstall Ltd.11.1.14 Mimetas Bv11.1.15 Tissuse Gmbh11.2 Other Players11.2.1 Hamilton Company11.2.2 Qgel Sa11.2.3 Lena Biosciences11.2.4 Cellendes Gmbh11.2.5 Uab Ferentis11.2.6 Greiner Bio-One International Gmbh11.2.7 Promocell Gmbh11.2.8 Advanced Biomatrix, Inc. (Part of Bico Group)11.2.9 Visikol, Inc. (Formerly Hurel Corporation)11.2.10 Synvivo Inc.

12 Appendix

For more information about this report visit https://www.researchandmarkets.com/r/v5sl9v

Read the rest here:
3D Cell Culture Market by Type, Application, End-user and Region - Global Forecast to 2027 - GlobeNewswire