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Cell Biology

NYC Mayor Eric Adams Joined Top Biomedical Researchers to Usher in the Center for Engineering and Precision – EIN News

New York City Mayor Eric Adams speaks at the grand opening for the Center for Engineering and Precision Medicine on March 29, 2023.

Rensselaer Polytechnic Institute President Martin A. Schmidt 81, Ph.D., and Center for Engineering and Precision Medicine Co-Director Jonathan Dordick, Ph.D., tour the new center during the March 29, 2023 grand opening in New York City.

Dennis S. Charney, M.D., the Anne and Joel Ehrenkranz Dean of Icahn Mount Sinai, speaks at the grand opening for the Center for Engineering and Precision Medicine on March 29, 2023 in New York City.

Center for Engineering and Precision Medicine Co-Directors Jonathan Dordick, Ph.D., and Priti Balchandani, Ph.D., at the grand opening on March 29, 2023.

Keynote speakers Derrick Rossi, Ph.D., Interim CEO of New York Stem Cell Foundation, and Roderic I. Pettigrew, Ph.D., M.D., CEO of Engineering Health, tour the Center for Engineering and Precision Medicine at its grand opening on March 29, 2023 in New York City.

Rensselaer Polytechnic Institute and the Icahn School of Medicine at Mount Sinai partner to advance medical research at life sciences hub

New York City Mayor Eric Adams

Rensselaer Polytechnic Institute and the Icahn School of Medicine at Mount Sinai partner to advance medical research at life sciences hub

The grand opening of the Center for Engineering and Precision Medicine (CEPM), a partnership between Rensselaer Polytechnic Institute (RPI) and the Icahn School of Medicine at Mount Sinai (Icahn Mount Sinai), was held yesterday at the Hudson Research Center (HRC) at 619 West 54th Street.

The center is the latest in a 10+ year partnership between RPI, a world-renowned technological research university known for its engineering, technology, and science programs, and Icahn Mount Sinai, the academic arm of the Mount Sinai Health System, which includes eight hospitals and a vast network of ambulatory practices throughout the greater New York City region. The HRC is a 320,000-square-foot, mixed-use hub for innovation in New York Citys growing life sciences sector.

We are thrilled to open the doors to the Center for Engineering and Precision Medicine, said Rensselaer President Martin A. Schmidt, Ph.D. CEPM will transform the diagnosis and treatment of cancer, Alzheimers, infectious diseases, and more by advancing state-of-the-art technologies and focusing on a personalized approach. CEPM, the third of RPIs New York City-based research centers, will also provide exceptional educational opportunities for the next generation of researchers, medical professionals, and life sciences entrepreneurs.

Leveraging the strength of RPI and Icahn Mount Sinai, CEPM bridges research, technology development and commercialization, and education. CEPM is one of the first life science centers of its kind in New York City and the nation to integrate engineering and biomedical sciences with education, training, and research collaborations to radically improve human health.

CEPM is built on the tenet that engineering is fundamental to understanding biomedical phenomena and developing the next generation of precision diagnostics and therapeutics for human health and well-being. RPI and Icahn Mount Sinai are well-positioned to seamlessly integrate research and education in engineering with medicine and transform personalized medicine. Critically, a major distinguishing feature of CEPM is the immense diversity in patients within the Mount Sinai Health System. This diversity, together with the analytical capabilities of engineering, is critical in advancing precision medicine.

The Center for Engineering and Precision Medicine combines the biomedical excellence of Icahn Mount Sinai with the engineering expertise of RPI to create an academic research hub that will make fundamental discoveries and develop new treatments that will improve the lives of patients suffering from the most complex diseases, said Dennis S. Charney, M.D., the Anne and Joel Ehrenkranz Dean of Icahn Mount Sinai.

Housed in 23,000 square feet of lab space on the 9th floor of the HRC, CEPM will benefit from the areas abundance of research talent and is in the process of recruiting faculty and staff. The space provides both wet lab and dry lab capabilities with high-performance computational infrastructure to seamlessly perform complex experiments and build advanced technologies to diagnose, treat, and manage diseases at a patients level. Office space and open cubicles surround the lab space to create a cohesive and collaborative research environment to promote interdisciplinary teamwork.

The Center for Engineering and Precision Medicine is more than a hub for research and education its a bridge to the future, said New York City Mayor Eric Adams. Our administration is harnessing the momentum of the life sciences industry to create access to next-generation jobs for everyone. Last year, Governor Hochul and I announced SPARC Kips Bay, an education and innovation hub that will be the first of its kind in New York City, which will generate $25 billion in economic impact to the city and create 10,000 jobs. Together, we are going to make sure New York City leads the globe in life sciences.

The New York Stem Cell Foundation (NYSCF) Research Institute, a nonprofit organization with a mission to accelerate cures for the major diseases of our time, is on the second and third floors of the HRC. Stem cell research plays a critical role in engineering tissue repair and in developing various cell types for drug discovery screening.

These two institutions are widely recognized leaders in engineering and medicine, and we are delighted to welcome the Center for Engineering and Precision Medicine to the Hudson Research Center by hosting the grand opening event, said Derrick Rossi, Ph.D., Interim CEO of NYSCF. The synergies between NYSCFs stem cell biology and the engineering and medical expertise at CEPM will lead to new and important collaborations to accelerate discoveries that directly reach patients.

Speakers included Schmidt and Charney, Mayor Adams, Senator Charles Schumer and Senator Kirsten Gillibrand (via video), and New York City Economic Development Corporation (NYCEDC) President and CEO Andrew Kimball.

As we continue to establish New York City as the leader in the life sciences industry, we must continue to bolster innovation that will create new jobs and spur meaningful research, said Kimball. The Center for Engineering and Precision Medicine will uniquely bridge biology, health care, and technology to advance cutting-edge discoveries and accelerate breakthrough treatment for intractable diseases, advancing individualized treatment, and improving quality of life for all New Yorkers. We are excited to continue working with our partners to spark new opportunities in this rapidly growing industry. The keynote speakers were Rossi and Roderic I. Pettigrew, Ph.D., M.D., CEO of Engineering Health and Executive Dean for Engineering Medicine at Texas A&M University, in partnership with Houston Methodist Hospital.

Additional speakers included CEPM Co-Directors Jonathan Dordick, Ph.D., Institute Professor of Chemical and Biological Engineering, Biomedical Engineering, and Biological Sciences at Rensselaer; and Priti Balchandani, Ph.D., Professor of Diagnostic, Molecular and Interventional Radiology, Neuroscience, and Psychiatry at Icahn Mount Sinai; as well as Deepak Vashishth, Ph.D., Director of the Center for Biotechnology and Interdisciplinary Studies at Rensselaer and CEPM Associate Director.

The Center for Engineering and Precision Medicine will enable breakthroughs in neuromodulation, immune resilience, and regenerative and reparative medicine, said CEPM Co-Director Dordick. We will give top talent with ambitious ideas the resources they need to more effectively advance personalized medicine to address intractable diseases and benefit patients.

CEPM represents the evolution of a successful partnership between Mount Sinai and Rensselaer that has secured over $80 million in shared research funding since 2013. CEPM will drive advances in point-of-care and point-of-use devices and diagnostics; microphysiological platforms for discovery and diagnosis; robotic surgery; biomedical imaging; therapeutics biomanufacturing; and artificial intelligence and machine learning applied to biomedical data. The Center for Engineering and Precision Medicine is creating a direct opportunity for exceptional engineers to apply their knowledge and skill toward the transformation of medicine and improvement of human health, said CEPM Co-Director Balchandani.

CEPM will offer a joint Ph.D. to train students in engineering medicine with expertise in reparative medicine, and neuro- and immuno- engineering through educational courses and research training. It will involve immersions in engineering, entrepreneurship and commercialization, and clinical rotation and shadowing to create a translational mindset at the onset of the program and produce a new breed of Ph.D.s capable of inventing new technologies to address unmet clinical needs. The development of certificate programs will broaden CEPMs academic mission and facilitate entrepreneurship and commercialization of advanced technologies and medical devices.

The Center for Engineering and Precision Medicine presents exciting opportunities for researchers, students, and, ultimately, patients, said Vashishth. The treatments and technologies developed at CEPM will decrease side effects and increase effectiveness for patients and usher an inclusive and healthier future for medicine and health care.

We are proud to welcome Rensselaer and Mount Sinai as they launch the new Center for Engineering and Precision Medicine in the Hudson Research Center, said Matthew Weir, President of Elevate Research Properties. This new center will serve as an important anchor for the growing New York City research ecosystem.

About Rensselaer Polytechnic Institute: Founded in 1824, Rensselaer Polytechnic Institute is Americas first technological research university. Rensselaer encompasses five schools, over 30 research centers, more than 140 academic programs, including 25 new programs, and a dynamic community comprised of over 6,800 students and 104,000 living alumni and alumnae. Rensselaer faculty and graduates include upward of 155 National Academy members, six members of the National Inventors Hall of Fame, six National Medal of Technology winners, five National Medal of Science winners, and a Nobel Prize winner in Physics. With nearly 200 years of experience advancing scientific and technological knowledge, Rensselaer remains focused on addressing global challenges with a spirit of ingenuity and collaboration. To learn more, please visit http://www.rpi.edu.

About the Icahn School of Medicine at Mount Sinai: The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the eight member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to a large and diverse patient population. Ranked 14th nationwide in National Institutes of Health (NIH) funding and among the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges, Icahn Mount Sinai has a talented, productive, and successful faculty. More than 3,000 full-time scientists, educators and clinicians work within and across 34 academic departments and 35 multidisciplinary institutes, a structure that facilitates tremendous collaboration and synergy. Our emphasis on translational research and therapeutics is evident in such diverse areas as genomics/big data, virology, neuroscience, cardiology, geriatrics, as well as gastrointestinal and liver diseases. Icahn Mount Sinai offers highly competitive MD, PhD, and Masters degree programs, with current enrollment of approximately 1,300 students. It has the largest graduate medical education program in the country, with more than 2,000 clinical residents and fellows training throughout the Health System. In addition, more than 550 postdoctoral research fellows are in training within the Health System. To learn more, please visit https://icahn.mssm.edu/.

About Taconic Partners: Since 1997, Taconic Partners has acquired, redeveloped and repositioned over 12 million square feet of commercial office and mixed-use space, as well as over 6,500 units of luxury and workforce housing. As a fully integrated real estate company with a keen eye for uncovering value, its diverse capabilities are evidenced by its multifaceted success with luxury properties, as well as adaptive reuse and urban revitalization projects. In New York City, Taconic is advancing over 650,000 square feet of life sciences space at 125 West End Avenue as well as at the Hudson Research Center at 619 West 54th Street. Other active Taconic projects include 817 Broadway, 311 West 42nd Street and Essex Crossing on the Lower East Side. The firm also manages various real estate funds on behalf of institutional and pension fund investors. For more information visit: http://www.taconicpartners.com

About Silverstein Properties: Silverstein Properties is a privately held, full-service real estate development, investment and management firm based in New York. Founded in 1957 by Chairman Larry Silverstein, the company has developed, owned and managed more than 40 million square feet of commercial, residential, retail and hotel space. Recent projects include 7 World Trade Center, the first LEED-certified office tower in New York City (2006), 4 World Trade Center (2013), the Four Seasons Downtown (2016), One West End (2017) and 3 World Trade Center (2018). The company has been recognized as one of the Best Places to Work in New York City by Crains New York Business for eight years in a row. For further information on Silverstein Properties, please visit http://www.silversteinproperties.com.

About New York Stem Cell Foundation Research Institute: The New York Stem Cell Foundation (NYSCF) Research Institute is an independent non-profit organization accelerating cures and better treatments for patients through stem cell research. The NYSCF global community includes over 200 researchers at leading institutions worldwide, including the NYSCF Druckenmiller Fellows, the NYSCF Robertson Investigators, the NYSCF Robertson Stem Cell Prize Recipients, and NYSCF Research Institute scientists and engineers. The NYSCF Research Institute is an acknowledged world leader in stem cell research and in the development of pioneering stem cell technologies, including the NYSCF Global Stem Cell Array, which is used to create cell lines for laboratories around the globe. NYSCF focuses on translational research in an accelerator model designed to overcome barriers that slow discovery and replace silos with collaboration.

Contact: Rensselaer Polytechnic Institute Katie Malatino malatk@rpi.edu 838-240-5691

Mount Sinai Karin Eskenazi karin.eskenazi@mssm.edu 332-257-1538

Taconic Partners/Silverstein Properties Johann Hamilton johann@relevanceinternational.com 917-887-1750

New York Stem Cell Foundation David McKeon dmckeon@nyscf.org 212-365-7440

Katie MalatinoRensselaer Polytechnic Institute+1 838-240-5691malatk@rpi.edu

Rensselaer Polytechnic Institute President Martin A. Schmidt 81, Ph.D., and Center for Engineering and Precision Medicine Co-Director Jonathan Dordick, Ph.D., tour the new center during the March 29, 2023 grand opening in New York City.

Dennis S. Charney, M.D., the Anne and Joel Ehrenkranz Dean of Icahn Mount Sinai, speaks at the grand opening for the Center for Engineering and Precision Medicine on March 29, 2023 in New York City.

Center for Engineering and Precision Medicine Co-Directors Jonathan Dordick, Ph.D., and Priti Balchandani, Ph.D., at the grand opening on March 29, 2023.

Keynote speakers Derrick Rossi, Ph.D., Interim CEO of New York Stem Cell Foundation, and Roderic I. Pettigrew, Ph.D., M.D., CEO of Engineering Health, tour the Center for Engineering and Precision Medicine at its grand opening on March 29, 2023 in New York City.

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NYC Mayor Eric Adams Joined Top Biomedical Researchers to Usher in the Center for Engineering and Precision - EIN News

Cell Biology

Funding boost for world-first cell transplantation research for … – The National Tribune

Griffith Universitys world-first study into cell transplantation to repair injuries to the nervous system has received a major boost thanks to a $5.4 million funding extension from the Motor Accident Insurance Commission (MAIC).

Griffiths Clem Jones Centre for Neurobiology and Stem Cell Research, headed by Professor James St John, is developing cell transplantation therapies to treat injuries of the nervous system.

Professor St John said spinal cord injury, peripheral nerve injuries and brain injuries are of particular concern for people who suffer road trauma and can leave victims with life-long paralysis and reduced quality of life.

The research team has created a world-first cellular nerve bridge technology which has already received two major national awards, the NHMRC Marshall and Warren Innovation Award 2019 and the Research Australia Discovery Award 2020-2021, he said.

The innovative technology enables the rapid generation of cellular nerve bridges which can be easily handled by surgeons for transplantation to treat spinal cord injury.

This latest round of funding will allow the research team to expand the nerve bridge technology to a wider range of nervous system injuries including peripheral nerve and brain injuries.

We are now on the verge of a human Phase 1 clinical trial for treating chronic spinal cord injury, and through the ongoing support of MAIC we are delighted we have been able to deliver it right here in Queensland.

The Clem Jones Centre team has successfully demonstrated the efficacy of the nerve bridges for treating spinal cord injury in preclinical models.

Professor James St John said the funding has enabled the team of more than 30 researchers to rapidly create, test and improve incredible technologies that were just a dream a few years ago.

By combining discovery research with translational research, we can fast-track the delivery of therapies to the clinic, Professor St John said.

Our research team is successful because of the diversity of our ideas.

Our team members come from 12 different countries, and we cover all areas of research from discovery cell biology, to bioengineering, surgery, rehabilitation and clinical trial planning.

It also means we can simultaneously develop and translate the research into clinical outcomes.

The new MAIC funding of $5.4 million brings the total MAIC investment into the therapy development to more than $16 million since 2017, with the major focus of the research being to develop a therapy for spinal cord injury.

Insurance Commissioner Neil Singleton said MAIC was delighted to continue to support Professor St John and his team in their potentially ground-breaking work.

Road trauma remains one of the leading causes of both spinal cord and brain injuries which can have devastating impacts on the lives of everyday Queenslanders and their families, Mr Singleton said.

Our continued support of this important research reflects our commitment to investing in initiatives which can make a real difference in mitigating the impacts of road trauma.

We are excited about the opportunities that may emerge as this research proceeds to a clinical trial in the near future.

The Clem Jones Centre for Neurobiology and Stem Cell Research was established in 2016 with funding from the Clem Jones Foundation ($2.4 million since 2016) with the aim of creating therapies to treat injuries and diseases of the nervous system.

The Centre is part of the Griffith Institute for Drug Discovery and the Menzies Health Institute Queensland, with the spinal cord project a legacy life-long project of the late Professor Emeritus Alan Mackay-Sim.

The Centre has also been strongly supported by the Perry Cross Spinal Research Foundation with more than $2 million in funding.

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Funding boost for world-first cell transplantation research for ... - The National Tribune

Cell Biology

Precigen Announces Further Advancement of UltraCAR-T Platform … – BioSpace

Milestone represents the first patient dosed with the next generation UltraCAR-T, incorporating PD-1 checkpoint inhibition in addition to three effector genes Proprietary technology for checkpoint blockade intrinsic to UltraCAR-T cells avoids the need for combination with a systemic checkpoint inhibitor, potentially limiting cost and systemic toxicity

GERMANTOWN, Md., March 29, 2023 /PRNewswire/ --Precigen, Inc.(Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, today announced that the first patient has been dosed in the Phase 1/1b dose escalation/dose expansion study (clinical trial identifier: NCT05694364) of PRGN-3007 in advanced ROR1-positive (ROR1+) hematological and solid tumors. The target patient population for the study includeschronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), acute lymphoblastic leukemia (ALL), and diffuse large B-cell lymphoma (DLBCL) and solid tumors, including breast adenocarcinomas encompassing triple negative breast cancer (TNBC). There are estimated to be more than 100,000 patients diagnosed in both the hematological and TNBC target populations in the United States, European Union and Japan in 2023.a

PRGN-3007 UltraCAR-T is a first-in-class investigational multigenic, autologous CAR-T cell therapy utilizing Precigen's clinically validated advanced non-viral gene delivery system and well-established overnight, decentralized manufacturing process. Precigen has further advanced the UltraCAR-T platform to address the inhibitory tumor microenvironment by incorporating intrinsic checkpoint blockade without the need for complex and costly gene editing techniques. PRGN-3007 is engineered using a single multicistronic transposon plasmid to simultaneously express a chimeric antigen receptor (CAR) targeting ROR1, membrane-bound interleukin15 (mbIL15), a kill switch, and a novel mechanism for the intrinsic blockade of PD-1 gene expression. The innovative design of PRGN-3007, where the blockade of PD-1 expression is intrinsic and localized to UltraCAR-T cells, is aimed at avoiding systemic toxicity and the high cost of checkpoint inhibitors by eliminating the need for combination treatment.

The Phase 1/1b clinical trial is an open-label study designed to evaluate the safety and efficacy of PRGN-3007 in patients with advanced ROR1+ hematological (Arm 1) and solid (Arm 2) tumors. The study is enrolling in two parts: an initial 3+3 dose escalation in each arm followed by a dose expansion at the maximum tolerated dose (MTD). Arm 1 and Arm 2 are enrolling in parallel. The investigator-initiated study is being conducted in collaboration with the H. Lee Moffitt Cancer Center & Research Institute (Moffitt).

"We are excited to work with Precigen and announce that the first patient, a CLL patient, has been dosed in the first-in-human study of PRGN-3007 UltraCAR-T," said Javier Pinilla-Ibarz, MD, PhD, Senior Member, Lymphoma Section Head and Director of Immunotherapy, Malignant Hematology Department, Moffitt, and Principal Investigator for the PRGN-3007 clinical study. "ROR1 is a promising target for addressing a wide variety of tumors and we are hopeful that the PRGN-3007 study will further the development of this novel CAR-T treatment, which combines intrinsic PD-1 inhibition and ease of administration from the validated overnight manufacturing of UltraCAR-T performed at our medical center bringing therapy to patients within one day."

"Dosing the first patient with PRGN-3007, the next generation of UltraCAR-T incorporating PD-1 inhibition, is a significant milestone for the UltraCAR-T platform," saidHelen Sabzevari, PhD, President and CEO ofPrecigen. "The PRGN-3007 study targets a broad range of hematological and solid tumor indications and this milestone helps us move closer to our vision for UltraCAR-T, which aims to deliver a library of personalized autologous UltraCAR-T therapies usingovernight manufacturingat the patient's medical center."

Precigen: Advancing Medicine with PrecisionPrecigen (Nasdaq: PGEN) is a dedicated discovery and clinical stage biopharmaceutical company advancing the next generation of gene and cell therapies using precision technology to target the most urgent and intractable diseases in our core therapeutic areas of immuno-oncology, autoimmune disorders, and infectious diseases. Our technologies enable us to find innovative solutions for affordable biotherapeutics in a controlled manner. Precigen operates as an innovation engine progressing a preclinical and clinical pipeline of well-differentiated therapies toward clinical proof-of-concept and commercialization. For more information about Precigen, visit http://www.precigen.comor follow us on Twitter @Precigen, LinkedInor YouTube.

About Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1)ROR1 is a type I orphan-receptor that is expressed during embryogenesis and by certain hematological and solid tumors but is undetectable on normal adult tissues.1-3 ROR1 plays an important role in oncogenesis by activating cell survival signaling events, particularly the non-canonical WNT signaling pathway.4 Aberrant expression of ROR1 is detected in multiple hematological malignancies including CLL5, MCL6, ALL7, and DLBCL.8 Elevated ROR1 expression is detected in various solid tumors, including breast adenocarcinoma encompassing TNBC, pancreatic cancer, ovarian cancer, Ewing's sarcoma and lung adenocarcinoma.9-14 Many human breast adenocarcinomas express high levels of ROR1, which is not expressed by normal breast tissue.15

UltraCAR-TUltraCAR-T is a multigenic autologous CAR-T platform that utilizes Precigen's advanced non-viral Sleeping Beauty system to simultaneously express an antigen-specific CAR to specifically target tumor cells, mbIL15 for enhanced in vivo expansion and persistence, and a kill switch to conditionally eliminate CAR-T cells for a potentially improved safety profile. Precigen has advanced the UltraCAR-T platform to address the inhibitory tumor microenvironment by incorporating a novel mechanism for intrinsic checkpoint blockade without the need for complex and expensive gene editing techniques. UltraCAR-T investigational therapies are manufactured via Precigen's overnight manufacturing process using the proprietary UltraPorator electroporation system at the medical center and administered to patients only one day following gene transfer. The overnight UltraCAR-T manufacturing process does not use viral vectors and does not require ex vivo activation and expansion of T cells, potentially addressing major limitations of current T cell therapies.

UltraPoratorThe UltraPorator system is an exclusive device and proprietary software solution for the scale-up of rapid and cost-effective manufacturing of UltraCAR-T therapies and potentially represents a major advancement over current electroporation devices by significantly reducing the processing time and contamination risk. The UltraPorator device is a high-throughput, semi-closed electroporation system for modifying T cells using Precigen's proprietary non-viral gene transfer technology. UltraPorator is being utilized for clinical manufacturing of Precigen's investigational UltraCAR-T therapies in compliance with current good manufacturing practices.

TrademarksPrecigen, UltraCAR-T, UltraPorator, and Advancing Medicine with Precision are trademarks ofPrecigenand/or its affiliates. Other names may be trademarks of their respective owners.

Cautionary Statement Regarding Forward-Looking StatementsSome of the statements made in this press release are forward-looking statements. These forward-looking statements are based upon the Company's current expectations and projections about future events and generally relate to plans, objectives, and expectations for the development of the Company's business, including the timing and progress of preclinical studies, clinical trials, discovery programs and related milestones, the promise of the Company's portfolio of therapies, and in particular its CAR-T and AdenoVerse therapies. Although management believes that the plans and objectives reflected in or suggested by these forward-looking statements are reasonable, all forward-looking statements involve risks and uncertainties, including the possibility that the timeline for the Company's clinical trials might be impacted by the COVID-19 pandemic, and actual future results may be materially different from the plans, objectives and expectations expressed in this press release. The Company has no obligation to provide any updates to these forward-looking statements even if its expectations change. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. For further information on potential risks and uncertainties, and other important factors, any of which could cause the Company's actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in the Company's most recent Annual Report on Form 10-K and subsequent reports filed with the Securities and Exchange Commission.

Referencesa GlobalData Epidemiology Market Size Research.1Balakrishnan, A., et al., Analysis of ROR1 Protein Expression in Human Cancer and Normal Tissues. Clin Cancer Res, 2017. 23(12): p. 3061-3071.2Green, J.L., et al., ROR receptor tyrosine kinases: orphans no more. Trends in Cell Biology, 2008. 18(11): p. 536-544.3Rebagay, G., et al., ROR1 and ROR2 in Human Malignancies: Potentials for Targeted Therapy. Front Oncol, 2012. 2(34).4Zhao Y, et al., Tyrosine Kinase ROR1 as a Target for Anti-Cancer Therapies. Front. Oncol, 2021.5Baskar, S., et al., Unique Cell Surface Expression of Receptor Tyrosine Kinase ROR1 in Human B-Cell Chronic Lymphocytic Leukemia. Clin Cancer Res, 2008. 14(2): p. 396-404.6Hudecek, M., et al., The B-cell tumorassociated antigen ROR1 can be targeted with T cells modified to express a ROR1-specific chimeric antigen receptor. Blood, 2010. 116(22): p. 4532-4541.7Enayati H, et al., Expression of ROR1 Gene in Patients with Acute Lymphoblastic Leukemia. IJBC 2019; 11(2): 57-62.8Ghaderi, A., et al., ROR1 Is Expressed in Diffuse Large B-Cell Lymphoma (DLBCL) and a Small Molecule Inhibitor of ROR1 (KAN0441571C) Induced Apoptosis of Lymphoma Cells. Biomedicines, 2020. 8(6).9Zhang, S., et al., The onco-embryonic antigen ROR1 is expressed by a variety of human cancers. Am J Pathol, 2012. 181(6): p. 1903-10.10Zhang, S., et al., ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth. PLoS One, 2012.7(3): p. e31127.11Potratz, J., et al., Receptor tyrosine kinase gene expression profiles of Ewing sarcomas reveal ROR1 as a potential therapeutic target in metastatic disease. Mol Oncol, 2016. 10(5): p. 677-92.12Zheng, Y.Z., et al., ROR1 is a novel prognostic biomarker in patients with lung adenocarcinoma. Sci Rep, 2016. 6: p. 36447.13Choi, M.Y., et al., Pre-clinical Specificity and Safety of UC-961, a First-In-Class Monoclonal Antibody Targeting ROR1. Clin Lymphoma Myeloma Leuk, 2015. 15 Suppl: p. S167-9.14Balakrishnan, A., et al., Analysis of ROR1 Protein Expression in Human Cancer and Normal Tissues. Clin Cancer Res, 2017. 23(12): p. 3061-3071.15Zhang S. et al., ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth. PLoS One, 2012, 7:e31127.

Investor Contact:Steven M. HarasymVice President, Investor RelationsTel: +1 (301) 556-9850investors@precigen.com

Media Contacts:Donelle M. Gregorypress@precigen.com

Glenn SilverLazar-FINN Partnersglenn.silver@finnpartners.com

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Cell Biology

Heart attack study could change the game in regenerative medicine – EurekAlert

image:Alexandre Colas, Ph.D. view more

Credit: Sanford Burnham Prebys

LA JOLLA, CALIF. Mar 29, 2023 -Sanford Burnham Prebys researchers have identified a group of proteins that could be the secret to cellular reprogramming, an emerging approach in regenerative medicine in which scientists transform cells to repair damaged or injured body tissues. The researchers were able to reprogram damaged heart cells to repair heart injuries in mice following a heart attack. The findings, which appear in the journalNature Communications, could one day transform the way we treat a variety of diseases, including cardiovascular disease, Parkinsons and neuromuscular diseases.

Even if a person survives a heart attack, there could still be long-term damage to the heart that increases the risk of heart problems down the line, says lead authorAlexandre Colas, Ph.D., an assistant professor in the Development, Aging and Regeneration Program at Sanford Burnham Prebys. Helping the heart heal after injury is an important medical need in its own right, but these findings also pave the way for wider applications of cell reprogramming in medicine.

Even though each of our cells has the same number of genesapproximately 20,000cells can select which genes to turn on and turn off to change what they look like and what they do. This is the foundation of cellular reprogramming.

Cellular reprogramming could, in theory, allow us to control the activity and appearance of any cell, says Colas. This concept has huge implications in terms of helping the body regenerate itself, but barriers to reprogramming mechanisms have prevented the science from moving from the lab to the clinic.

The researchers identified a group of four proteins, named AJSZ, that help solve this problem.By blocking the activity of these proteins, we were able to reduce scarring on the heart and induce a 50% improvement in overall heart function in mice that have undergone a heart attack, says Colas.

Although the researchers were primarily focused on heart cells, they determined that AJSZ is universal to all cell types. This suggests that targeting AJSZ could be a promising treatment approach for a variety of human diseases.

This is helping us solve a very big problem that a lot of researchers are interested in, says Colas. Even more important, this breakthrough is a significant step forward on our way to turning these promising biological concepts into real treatments.

The next steps in translating their discovery into a potential treatment is to explore different ways of blocking the function of the AJSZ proteins. According to Colas, the most promising option would be to use a small molecule drug to block the activity of AJSZ.

We need to find a way to inhibit these proteins in a way we can control to make sure we are only reprogramming the cells that need it, says Colas. We will be screening for drugs that can help us inhibit these proteins in a controlled and selective manner in the coming months.

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Additional authors of the study include Maria A. Missinato, Michaela Lynott, Michael S. Yu, Anas Kervadec, Yu-Ling Chan, Christopher Lee, Prashila Amatya, Hiroshi Tanaka, Chun-Teng Huang, Pier Lorenzo Puri, Peter D. Adams and Alessandra Sacco, Sanford Burnham Prebys; Sean Murphy, Suraj Kannan, Chulan Kwon and Peter Andersen, Johns Hopkins University School of Medicine; and Li Qian, University of North Carolina at Chapel Hill.

The study was supported by grants from the California Institute of Regenerative Medicine (DISC2-10110), the National Institutes of Health (R01 HL153645, R01 HL148827, R01 HL149992, R01 AG071464), and Sanford Burnham Prebys institutional support to Alexandre Colas.

The studys DOI is 10.1038/s41467-023-37256-8.

About Sanford Burnham Prebys

Sanford Burnham Prebys is an independent biomedical research institute dedicated to understanding human biology and disease and advancing scientific discoveries to profoundly impact human health. For more than 45 years, our research has produced breakthroughs in cancer, neuroscience, immunology and childrens diseases, and is anchored by our NCI-designated Cancer Center and advanced drug discovery capabilities. For more information, visit us atSBPdiscovery.orgor on Facebookfacebook.com/SBPdiscoveryand on Twitter@SBPdiscovery.

Nature Communications

Conserved transcription factors promote cell fate stability and restrict reprogramming potential in differentiated cells

27-Mar-2023

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Heart attack study could change the game in regenerative medicine - EurekAlert

Cell Biology

20-Year Study May Upend Long-Held Theory About Chromosomes and Cancer – Newswise

FOR IMMEDIATE RELEASE

Newswise Johns Hopkins Medicine scientists say their 20-year study of more than 200 people with premature aging syndromes caused by abnormally short telomeres, or shortened repetitive DNA sequences at the ends of chromosomes, may upend long-held scientific dogma and settle conflicting studies about how and whether short telomeres contribute to cancer risk.

The research, which has the potential to guide treatments and cancer screening among people with short telomere syndromes, appears in the April 10 issue of Cancer Cell.

For decades, some studies in animal models and cells have linked the existence of extremely short telomeres with instability of chromosomes, the X-shaped structures that house genes. Such instability is a common feature of cancer cells.

The new study suggests that chromosomal instability may not be the reason that people with short telomere syndromes are prone to a small but increased risk of certain types of solid cancers. Rather, the researchers say cancer predisposition in these patients may be linked to immune system cells that age and die or vanish prematurely.

This study reinforces how incredibly important the immune system is in surveilling our cells for cancer as we age, says Mary Armanios, M.D., professor of oncology and director of the telomere center at the Johns Hopkins Kimmel Cancer Center, and professor of genetic medicine, molecular biology and genetics, and pathology at the Johns Hopkins University School of Medicine.

Telomeres naturally shorten with age. People whose telomeres are highly truncated at or below the 10th percentile of human telomere lengths have some traits of premature aging. Their hair turns gray at a young age, for example, and they develop pulmonary fibrosis, or scarring of the lungs, earlier than most people do.

While short telomere syndromes are relatively rare, its estimated that some 50% of people with the most common type of pulmonary fibrosis have short telomeres.

For the new study, Armanios and pediatric oncologist Kristen Schratz, M.D., kept track of some 226 people with short telomere syndromes seen and diagnosed at The Johns Hopkins Hospital and other hospitals across the U.S. between 2003 and 2022. More than half of the participants were male, and their median age was 50 by the end of the study.

Over the two decades, 35 people (15%) in the group developed cancer, nearly all identified in adulthood. Twenty-one had blood cancers, either myelodysplastic syndrome or acute myeloid leukemia, both of which have long been associated with short telomere syndromes.

Of the 35, 14 developed 16 solid tumors, and 14 of them were squamous cancers, including those of the mouth, anus and skin that may also develop in people whose immune systems are suppressed. Half of these cancers were diagnosed early and were removed by surgery.

The number of cancers was lower than what would be expected if short telomeres fueled genome instability, and these are not the types of cancers youd expect in people with syndromes that mimic premature aging, says Armanios.

In addition, most of the patients who developed solid tumors (13 of 14) were males, and the molecular reasons why males with short telomeres tend to develop these tumors is worth further study, says Armanios.

During the 20-year span, population statistics suggest the 226 people in the study should have experienced about 19 cases of the most common lethal cancers mostly associated with aging, including lung, colon, pancreatic, kidney, bladder and uterine cancers.

The researchers sequenced the whole genome of eight of the squamous cancers to look for chromosomal instability, and found no parts of chromosomes had become fused or swapped with other chromosomes, which are major hallmarks of chromosomal instability. In fact, these cancers seem to have less chromosomal instability than comparable squamous cancers that arise in people without short telomere syndromes, says Armanios.

Looking more closely at the immune systems of the 14 patients with squamous cancers, 12 had levels of T-cells that were several standard deviations below the median range for people.

In a related set of experiments with a group of mice genetically engineered to have short telomeres, the researchers found low quantities of cancer-fighting immune cells, similar to levels in people with short telomeres. Mice with short telomeres were not able to fight off implanted cancers long term nor could they recruit T-cells effectively to the tumor site.

Our data suggest people with short telomeres may have a lower incidence of most cancers with some cancers arising in a small subset, says Armanios, who adds that short telomeres may not destabilize peoples genomes but, in rare cases, affect the capacity of T-cells to expand and maintain their memory to fight cancer in the long-term.

Armanios says the findings will help physicians target cancer screening to high-risk individuals with short telomeres and avoid exposing them to excess immunosuppressive drugs known to increase their risk for infection.

In addition to Armanios and Schratz, other researchers contributing to the study are Diane Flasch, Wentao Yang and Jinghui Zhang from St. Jude Childrens Research Hospital; Robert Vonderheide from the University of Pennsylvania; and Christine Atik, Zoe Cosner, Amanda Blackford, Dustin Gable, Paz Vellanki, Zhimin Xiang, Valeriya Gaysinskaya and Lisa Rooper from Johns Hopkins.

Funding for the research was provided by the National Institutes of Health (R01CA225027, R01HL119476, P30CA006973, T32GM007309, T32CA009071, F32HL142207, R01CA229803), Gary Williams Foundation, S&R Foundation, the Commonwealth Foundation, Godrej Industries, the Harrington family, the ASH Scholar Award, the Dresner Foundation and the Turock Scholars Fund.

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20-Year Study May Upend Long-Held Theory About Chromosomes and Cancer - Newswise

Cell Biology

Kenworthy links quantity to theory – ASBMB Today

Anne Kenworthy began doing lab science as an undergraduate at Kenyon College in Gambier, Ohio, but it was only after she moved on to graduate school and postdoctoral opportunities that she realized the breadth of research at R1 institutions.

Kenworthy began doing biophysical studies as a grad student in the cell biology department at Duke University. Her advisor, Tom McIntosh, was a physicist by training and was known for his work investigating the forces between bilayers in the cell membrane.

Anne Kenworthy

I found that work appealing, Kenworthy said. It was very quantitative, and I enjoyed being able to take measurements that you could then relate back to a physical theory.

Now a professor of cell biology and molecular physiology and biological physics at the University of Virginia School of Medicine, Kenworthy is the recipient of the American Society for Biochemistry and Molecular Biologys 2023 Mildred Cohn Award in Biological Chemistry. The award is named for the first female president of the ASBMB and honors scientists who have used innovative physical approaches to understand biological chemistry.

Kenworthy was nominated by Avril Somlyo, a UVA School of Medicine colleague WHO was previously Cohns colleague at the University of Pennsylvania, for her contributions to the study of membrane structure and dynamics, including being one of the first researchers to apply fluorescence resonance energy transfer, or FRET, microscopy to the study of lipid rafts.

Knowing Anne and having known Mildred as a colleague at the University of Pennsylvania, I believe it is an ideal match, Somlyo wrote.

I honestly couldnt believe it, Kenworthy said of winning the award. Sometimes you dont realize the impact that some of your discoveries have actually made.

In addition to her research, Kenworthy serves as an associate editor in the Cell Biophysics section of the Biophysical Journal and as faculty in the FLIM (fluorescence lifetime imaging microscopy) and FRET workshop at the Keck Center for Cellular Imaging at UVA. She considers it a natural part of her evolution as a researcher to contribute to the community by serving on editorial boards and study sections.

You have an important role in helping to make sure that applicants get fair reviews, Kenworthy said. You know that the best science can go on for funding agencies to make those final decisions.

Anne Kenworthys lab in the Center for Membrane and Cell Physiology at the UVA School of Medicine studies cell membranes and the microdomains inside them, such as lipid rafts. Lipid raft microdomains contain certain concentrations of proteins in a small area that allow them to perform activities such as signaling and extracellular sensing. Caveolae, a special type of lipid raft, are dips in the plasma membrane that are built by caveolin proteins and that function in signaling and lipid homeostasis. Together with collaborators, the Kenworthy lab recently determined a high-resolution cryo-electron microscopy structure of the 3D form of a caveolin protein, a landmark achievement.

The lab also studies the structure and dynamics of lipid rafts themselves using techniques such as quantitative fluorescence microscopy, where the brightness level of fluorescence proteins is given a number compared to a control level of brightness and undergoes mathematical model analysis. Using florescence, the Kenworthy lab can measure on and off rates of transient protein binding events and measure the diffusion rate of lipids and proteins in the membrane.

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Kenworthy links quantity to theory - ASBMB Today

Cell Biology

Biology Alumna Named Conn.’s Teacher of the Year – Susquehanna University

October 13, 2022

What keeps Carolyn Kuhr 98 Kielma coming back to teaching year after year is not the biology content she teaches, but the connections she shares with her students.

Kielma was named Connecticuts Teacher of the Year by Gov. Ned Lamont and the Connecticut State Department of Education. She teaches biology and biotechnology and forensics at Bristol Eastern High School.

I am elated and honored to represent my students and my city, Kielma said. The longer the dust settles, the more overwhelmed with gratitude I am. So many former students, colleagues and parents are reaching out to congratulate me and wish me luck. I had no idea how much I was able to impact my community.

Growing up, Kielma said she was a curious child with an early passion for learning. Upon graduating from Susquehanna University, she worked several concurrent jobs while saving up to continue her education at graduate school which she did, graduating in 2002 with a Master of Education from the University of New Haven.

After my first few years in the profession, I discovered that learning science is not truly the goal for my students, Kielma said. I now believe teaching is not only about the content but about helping youth become better humans. I strive to be the type of teacher that I needed in my adolescent years the trusted adult that students can come to when they need help, whether inside or outside the classroom.

Now 20 years into her career, Kielma said she still gets excited when chatting with her current students about the research opportunities they could have if they find mentors like the ones she had at Susquehanna, including Jack Holt, professor of biology; Peggy Peeler, Charles B. Degenstein professor of biology; Tom Peeler, associate professor emeritus of biology; and David Richard, presidential professor of biology.

I will never forget being able to keep frog hearts beating in culture on a petri dish during cell biology lab and trudging through the waters collecting samples from the Susquehanna River during limnology, she said. They supported me by believing in me, even when I didnt. Thats one of the most important gifts I can give my current students too.

Kielma also believes in students shes never met those at Susquehanna who are just on the precipice of beginning their own careers in teaching.

I think the greatest advice I can offer is to be patient with yourself honing a craft like education takes time. Lean into the educators in your building; within your school will be a group of highly educated, motivated and courageous professionals who understand the power of lifelong learning. Trust in them and trust in yourself, Kielma said. Remember to stay positive and do not get caught up in negativity because you are making a difference, even if it is with one student at a time.

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Biology Alumna Named Conn.'s Teacher of the Year - Susquehanna University

Cell Biology

What does biochemistry have to do with climate change? – ASBMB Today

Ask Karla Neugebauer about her journey to climate activism, and she highlights two moments.

The first was in 2006. She was on vacation in Australias Northern Territory with her family, camping in the outback not far from Alice Springs. That part of Australia, known to some as the Red Centre, is beautiful, severe desert country the kind of place where its unwise to start a road trip without a five-gallon water tank and a spare tire. The rocks are russet. In the deep shade of narrow gullies in the MacDonnell mountain range, small pools of water cool the air around them, making small miracles of oasis.

Yale University

Karla Neugebauer's interest in climate change was inspired by a driving tripin the Australian outback and a dinner conversation with her son.

Neugebauer read aloud on the road trip, as she often did when her children were young. She came to an article by paleontologist turned climate writer and activist Tim Flannery outlining the fiery future Australia faced if it maintained its inaction on climate change.

Being immersed in the natural environment and then reading this thing was just kind of devastating, Neugebauer said. I remember sitting in the back seat and just bawling.

At the time, she was a group leader at the Max Planck Institute of Molecular Cell Biology and Genetics in Germany. There was no clear link between her professional expertise, which concerns RNA splicing and gene expression, and the looming crisis.

More than decade later, she sat down to dinner with her son and a friend he had grown up with. The world had continued to careen down the path of escalating emissions and rising global temperatures Flannery had described. Neugebauer had moved to the U.S. by this time and had taken a faculty position at Yale, but her son, a young adult, had returned to Dresden for an internship. He and his friend had become involved in the Fridays for Future climate protests; sometimes, their friends had been arrested. If they did choose to go to college, both young men said, the only fields worth studying would be environmental engineering or politics disciplines that could save the planet.

Their deep concern for the future galvanized her to act and made her wonder why other areas of expertise did not also seem like productive tools for climate activists. It disappointed me that other disciplines didnt come to their minds, Neugebauer said.

The more closely she looked at biochemistry, the less she could blame young people for overlooking its relevance. When she canvassed other universities for ideas about how to teach the biology of climate science, she came up emptyhanded. At interdepartmental meetings she began to attend virtually a few years later, during the pandemic, she was the only biochemist in attendance.

Neugebauer argues that the field has become myopically focused on human health because of funding organized around diseases of individual organs. Even basic researchers must think and write in terms of curing disease to secure grants.

I submit to you the work Im doing on stress in HeLa cells is relevant to climate change because Im studying how gene expression changes to parameters that are going to change for the algae and the fish, Neugebauer said. Yet when she talks to her neighbors about her work, she hears herself describing applications in cancer. Im not curing cancer! Im a basic scientist. Im asking fundamental questions that I believe are terribly important for allof these reasons.

She illustrated that belief by launching an unconventional seminar in the fall of 2021. The course, called Biochemistry and our Changing Climate, explores the basic biochemistry that governs living systems response to a changing world.

Neugebauer guides her students through discussions of articles that illuminate the core concepts of biochemistry in a climate context. She talks about the aromatic amino acid synthesis pathways that the pesticide Roundup inhibits and about how cell biological responses to heat stress contribute to coral bleaching. She talks about nitrogen fixation a biochemical process that her departments core courses do not cover. She talks about engineering enzymes that could recycle plastics or entomb atmospheric carbon in building materials.

Karla Neugebauer

In her course, Karla Neugebauer encourages students to propose research projects that would answer open questions about the links between biochemistry and climate change such as why red algae reduces cows methane emissions.

People have a hard time understanding what I mean by a class about biochemistry and climate change, she said. The course isnt focused on ecology or on bioengineering. Instead, she seeks to explore on a molecular level the mechanisms by which climate change is affecting and will alter further the living world. It frustrates her when students ask questions that biochemistry clearly could answer for example, What molecule from red algae reduces cows methane emissions? but has not.

She aims to show her students that biochemists have a role to play in understanding climate change and a role to play in adapting to and mitigating the crisis.

Neugebauer has spent time recently visiting other departments to tell them about her course. By the time you receive this magazine, she will be immersed in teaching it for a second time. Im on a mission to make people aware of this, she said.

Karla Neugebauer and Henry Jakubowski (author of the climate change article How to be a climate activist) will host an interest group on Biochemistry and Climate Change on March 25 at Discover BMB 2023, the ASBMB annual meeting in Seattle.

Originally posted here:
What does biochemistry have to do with climate change? - ASBMB Today

Cell Biology

Newly identified process keeps some immune cells on their toes – News-Medical.Net

Cancer cells use an unusual mechanism to migrate into new tissue and form metastases there. The same process probably also keeps some immune cells on their toes. This is the result of a recent study led by the University of Bonn. According to the study, certain structures, the centrioles, increase in number. This makes it easier for them to maintain their direction and thus migrate more quickly to the lymph nodes, where they activate other immune cells. The results have now been published in the Journal of Cell Biology.

Like the police, the immune system relies on division of labor. First of all, there are the dendritic cells. They search the tissue around the clock for traces of suspicious intruders, called antigens. If they are successful, they rush to the lymphatic vessels and from there to the draining lymph nodes. There they present their findings to a powerful search team, the T cells. These endogenous troops now know which enemy to fight.

This attack must take place before the invaders cause major damage or multiply too much. It is therefore important that dendritic cells migrate as quickly as possible to the briefing in the lymph node.

We have discovered a mechanism that helps them doing this. To do so, they form more of certain structures called centrosomes. These help them maintain their direction for longer and thus reach the lymphatic vessels more quickly."

Prof. Dr. Eva Kiermaier, LIMES Institute (Life and Medical Sciences), University of Bonn

Centrosomes belong to the organelles - these are molecular complexes that are responsible for specific tasks in cells, much like the organs in the body. Normally, there is exactly one centrosome in each human cell. Shortly before cell division, it doubles. The two copies migrate to opposite poles of the cell and stretch a bundle of fibers between them, the microtubules. With them, they pull the chromosomes (which have also doubled) apart during division. Each of the resulting daughter cells thus receives a complete set of genetic material as well as one of the two centrosomes.

"However, centrosomes are also responsible for organizing the cytoskeleton during cell migration," emphasizes Kiermaier, who was brought to the Rhine from Lower Austria (IST Austria, Klosterneuburg) in 2017 through the returnee program of the state of North Rhine-Westphalia. "By this we mean fiber-like structural proteins that give the cell its shape and provide it with stability." The cytoskeleton also decides where "front" and "back" are in a cell. And that, in turn, affects its direction of movement. "We have now been able to show that dendritic cells form multiple centrosomes as soon as they come into contact with an antigen," says Ann-Kathrin Weier. The PhD student at the LIMES Institute shares first authorship of the publication with her colleague Mirka Homrich. Both performed important parts of the experiments.

Dendritic cells have a problem: they do not know where the next lymphatic vessel is via which they can reach the lymph node. In their search, they proceed according to the strategy of "trial and error": they run in one direction for a short while and then change it if they have not encountered a vessel in the process. "The more centrosomes they have, the longer they stay on course before continuing to search in a different direction," says Mirka Homrich. "We were able to show in computer simulations that this allows them to find the lymphatic vessels much faster than they normally would." In the process, the proliferation of centrosomes adjusts their staying power just right - so they don't stick too stubbornly to their direction. This would increase the risk of them going astray and getting completely lost.

The mechanism identified in the study was previously completely unknown in healthy cells. Cancer cells were assumed to use it to form metastases. However, the multiplied centrosomes must not be freely distributed inside the cells. Otherwise, they would severely disrupt functions such as cell division. In both tumor and dendritic cells, the organelles therefore congregate at a single site - they cluster. "There are now agents that disrupt this clustering of centrosomes," says Kiermaier, who is also a member of the ImmunoSensation2 Cluster of Excellence and the Transdisciplinary Research Area "Life and Health" at the University of Bonn. "As a result, the cancer cells can no longer divide correctly, but die."

However, it is also possible that these substances interfere with the immune system - after all, the centrosomes cluster there as well. "We've tested several of these agents in cell cultures," she says. "We've actually found evidence that they could significantly impair the effectiveness of the immune defense." If that will be confirmed in clinical trials, it would be bad news as there could be considerable side effects if the active substances were used in cancer therapy.

In addition to the University of Bonn, the Charles University in Vestec, Czech Republic, and the Institutes of Science and Technology in Austria and Spain were involved in the work.

Source:

Journal reference:

Weier, A-K., et al. (2022) Multiple centrosomes enhance migration and immune cell effector functions of mature dendritic cells. Journal of Cell Biology. doi.org/10.1083/jcb.202107134.

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Newly identified process keeps some immune cells on their toes - News-Medical.Net

Cell Biology

Plants use their roots to measure manganese concentration available in the soil – EurekAlert

image:Arabidopsis seedlings have been exposed to manganese deficiency, and cytosolic calcium dynamics have been visualized utilizing the GCaMP6f-mCherry calcium biosensor. The calcium dynamics in roots are presented as false color images for selected timepoints after onset of manganese deficiency (from left). view more

Credit: University of Mnster - Kudla Group

Every living organism needs the element manganese as an essential nutrient. In plants, for example, it plays a major role in breaking down water into oxygen and hydrogen during photosynthesis. A team of German and Chinese researchers are the first to demonstrate, using the model species thale cress (Arabidopsis thaliana), how plants sense manganese deficiency and which processes then take place in the plant at the molecular level. The researchers showed that a hitherto undetected group of cells in the plant root plays a decisive role. The researchers hope that the results of their work will in the future lead to methods for making plants more resistant to manganese deficiency a condition which often occurs in alkaline and calcareous soils.

Prof. Jrg Kudla from the Institute of Plant Biology and Biotechnology at the University of Mnster (Germany) is one of the leading authors of the study and, as he says, There have been a lot of studies focusing on which proteins are involved in the uptake and transportation of manganese within a cell. But how the manganese balance is regulated at the level of the organism is completely unknown. Because calcium is involved as a messenger substance in numerous other regulating processes in the plant, the researchers asked themselves whether it also plays a role in regulating the manganese balance.

Manganese deficiency triggers oscillating calcium signals

The team identified a special cell group in the plant root and gave it the name manganese-sensitive niche. Unlike all other root cells, these cells display a special reaction in response to manganese deficiency: the calcium concentration within the cells rises and falls, several times in succession, as long as the deficiency lasts. Every oscillation lasts approximately 30 minutes. Nobody had previously observed such multi-cellular oscillations in the calcium concentration which are built up through the coordinated occurrence of calcium signals in individual cells in plants, says Kudla. Just a few hundred cells jointly build up the signal. The epidermal cells the cells in the outermost root layer are the first to begin increasing the calcium concentration. Then the cells situated further inside gradually follow suit before the whole process is then reversed.

Third stimulus-specific sensitive niche now discovered

In earlier work, researchers led by Jrg Kudla had already discovered two further sensitive niches in other areas in the root a potassium-sensitive niche and a sodium-sensitive niche. Here, too, the roots reacted by producing multicellular calcium signals in specific cell groups in response to changes in the ion concentrations in the environment. However, the researchers did not observe any oscillations unlike in the manganese-sensitive niche.

In their current study, the researchers discovered that the calcium oscillations triggered by manganese deficiency activate two special enzymes so-called Calcium-Dependent Protein Kinases (CPK21 and CPK23) and that these two enzymes, for their part, stimulate the uptake of manganese. As the kinase frees itself from the calcium, and these again become inactive. Our hypothesis is that every oscillation starts this process anew until the plant has achieved a sufficient uptake of manganese, says Kudla. The manganese transporter NRAMP1, which is responsible for transporting the manganese into the cells of the root, is part of the process. The protein kinases CPK21 and CPK23 interact with this transporter and regulate the uptake of manganese by phosphorylating one specifc amino-acid (Thr498).

In order to demonstrate the occurrence of the calcium signals, the researchers used high-resolution microscopy and, for the first time, ultra-sensitive molecular calcium-biosensors. Biosensors generally visualise changes in concentrations of bioactive substances such as calcium in cells and tissues. The team combined these studies, involving in vivo biosensor technology, with genetic, cell-biological and biochemical methods in order to clarify the underlying molecular mechanisms. In addition to the Mnster researchers, scientists from the College of Life Sciences, Northwest A&F University in Shaanxi and the Biotechnology Research Institute, Chinese Academy of Agricultural Sciences in Beijing (China) as well as from the Martin Luther University Halle-Wittenberg (Germany) were also involved.

Proceedings of the National Academy of Sciences

Experimental study

Not applicable

Ca-dependent phosphorylation of NRAMP1 by CPK21 and CPK23 facilitates manganese uptake and homeostasis in

30-Sep-2022

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Plants use their roots to measure manganese concentration available in the soil - EurekAlert