April 2024

NEWSLETTER

SHIFTING FOCUS: INVESTIGATORS DESCRIBE CHANGES TO PANCREATIC β CELL

AT ONSET OF TYPE 1 DIABETES

In our study, we investigated how a specific RNA modification, N6-methyladenosine (m⁶A), impacts Type 1 diabetes (T1D) onset. We found that m⁶A acts as a novel β-cell safeguard mechanism, controlling the strength and duration of the innate antiviral immune response. We observed that the levels of an enzyme responsible for adding m⁶A, called METTL3, increase significantly at T1D onset in human and mouse β-cells. Using a technique called m6A-sequencing, we discovered that certain genes involved in the innate antiviral immune response including 2'-5'-oligoadenylate synthetase (OAS) and adenosine deaminase RNA specific (ADAR1) become excessively methylated at T1D onset. By reducing METTL3 levels, we found that the stability of OAS increases, suggesting that METTL3 normally accelerates its decay. Importantly, in experiments employing a mouse model of T1D (NOD), we showed that prolonging METTL3 expression specifically in β-cells delays the onset of diabetes. We also uncovered that certain chemical signals in the cells, such as reactive oxygen species and nitric oxide, influence METTL3 activity. Additionally, we identified specific parts of the METTL3 protein that are sensitive to redox chemical modifications and play a role in controlling the stability of immune-related genes. Overall, our findings demonstrate that m⁶A modification is crucial for regulating the immune response in β-cells during the early events of T1D.

Manuscript information: Redox regulation of m6A methyltransferase METTL3 in β-cells controls the innate immune response in type 1 diabetes. Dario F. De Jesus, Zijie Zhang, Natalie K. Brown, Xiaolu Li, Ling Xiao, Jiang Hu, Matthew J. Gaffrey, Garrett Fogarty, Sevim Kahraman, Jiangbo Wei, Giorgio Basile, Tariq M. Rana, Clayton Mathews, Alvin C. Powers, Audrey V. Parent, Mark A. Atkinson, Sirano Dhe-Paganon, Decio L. Eizirik, Wei-Jun Qian, Chuan He, Rohit N. Kulkarni. Nature Cell Biology 2024: 421-437 PMID: 38409327

TIPS FOR THE NIH DATA SHARING MANDATE

Reoccurring Series

Tip #9: Does the Genomic Data Sharing Policy Apply to My Research? 

It is crucial for researchers to learn which research projects do and do not fall under the NIH genomic data sharing policy. NIH GDS policy applies to research that is both funded by the NIH and generate a large-scale human or non-human genomic data. Examples of such data include but are not limited to: sequence data from more than 100 isolates from infectious organism, data from 300,000 or more variant sites in more than 1,000 human research participants, whole genome or exome sequence data of more than one model organism species or strain, and much more. Click HERE for the full list of examples. There are a few examples where a project generated genomic data but is not within the policy’s intended scope, such as: instrument calibration exercises, statistical or technical methods development, and the use of genomic data for control purposes, such as for assay development. 

Click HERE for the detailed NIH report highlighting which projects do and do not fall under the scope of the NIH GDS policy.  

UPCOMING dkNET WEBINAR

The next dkNET Webinar "Using Texera to Support Collaborative Data Analysis for Diabetes Researchers"

will be held on Friday, April 26, 2024, 11 am - 12 pm Pacific.

Presenter: Chen Li, PhD, University of California, Irvine

To register click HERE.

UPCOMING MEETINGS

The European Islet Study Group (EISG) meeting has been organized almost every year since 1991. After the 2023 meeting in Vancouver, the EISG returns to Europe where the meeting will be held in Helsinki, Finland, June 18-20, 2024. The meeting program will highlight important scientific developments of all aspects of pancreatic islet biology. For more information click HERE.

The Midwest Islet Club Meeting will be held at the University of Chicago from July 10 - 11, 2024. For more information click HERE.

The Western Region Islet Study Group Annual Meeting (WRISG) will be held at the Asilomar Hotel and Conference Grounds in Pacific Grove, CA from October 16-18, 2024. Please contact meeting organizers via email with questions.

nPOD Type 1 Diabetes Key Questions Initiative

At nPOD we believe that through collaboration we can address critical issues in the science of type 1 diabetes. For this purpose, nPOD has announced formation of six new working groups, each aimed at addressing important topics that nPOD has identified as Key Questions in the field of T1D research. If you are passionate about making a difference through research, we invite you to join our new working group teams. As a member of one of these groups, you will have the opportunity to:

• Engage in groundbreaking research projects and work alongside experienced researchers and professionals who are leaders in their respective fields.
• Contribute to publications and presentations that showcase your findings to the wider scientific community.
• Make a meaningful impact by generating insights and solutions that drive positive change.

We know that diversity enriches our research community. Whether you're a seasoned researcher or just starting out in your career, we welcome individuals who are enthusiastic, innovative, and driven to excel. If you are interested in participating in new nPOD working groups, please visit our website to learn more and sign up to participate.

Join us in shaping the future through research!

THE SUGAR SCIENCE: WEEK IN REVIEW (WiR)

The T1D Week in Review (T1D WiR) is a Friday Weekly Newsletter providing recent updates in T1D research including top T1D weekly papers in many categories, T1D jobs, grant deadlines, hot ticket events, business updates plus this week’s watch and listen all provided by The Sugar Science. The most recent edition includes T1D updates from the past week.

To subscribe click HERE and to ask the experts click HERE.

NIH FUNDING OPPORTUNITIES

NOT-DK-24-001: Notice of Intent to Publish a Funding Opportunity Announcement for Cardiovascular Repository – Type 1 Diabetes (CARE-T1D) Consortium (U01 Clinical Trial Not Allowed)

• Application due date: April 11, 2024
• Foreign applications allowed

RFA-DK-23-007: Discovery of Early Type 1 Diabetes Disease Processes in the Human Pancreas [HIRN Consortium on Beta Cell Death and Survival (CBDS)] (U01 Clinical Trial Not Allowed)

• Application due date: July 10, 2024
• Foreign applications are not allowed

PAR-23-237: Enhancement and Management of Established Biomedical Data Repositories and Knowledgebases (U24 Clinical Trial Not Allowed)

• Application due date: Standard Dates
• Foreign applications allowed

Below is a summary of the most recent job postings by category (Faculty, Research Staff/Admin, Postdoc). Visit the HIRN Website for a full listing of job opportunities.

RESEARCH STAFF/ADMIN

Senior Research Investigator

Senior Investigator will lead ongoing research projects and the staff of NIH-sponsored beta-cell biology projects. Ensure the successful execution of ongoing studies, analyze the scientific results to prepare presentations and write manuscripts based on those results. Supervise existing laboratory staff, including facilitation, documentation, analysis and communication needed for ongoing laboratory work on behalf of the Principal Investigator.  For more information, please click HERE.

Postdoctoral Position

The Greiner and Brehm Labs at the UMass Chan Medical School’s Diabetes Center of Excellence in Worcester, MA is recruiting a fully funded postdoctoral position. Their laboratories specialize in humanized mouse models to study type 1 diabetes. Interests include effector functions of human autoreactive T cells, interactions between T cells and beta cells, and identifying immune therapeutics that suppress beta cell destruction. Approaches used included immunological, cellular, molecular, and genomic. For more information, please contact Dr. Michael Brehm directly.

Postdoctoral Position

The Université Libre de Bruxelles center for Diabetes is searching for a motivated PhD student to join a fully funded 4-year project. The loss of functional beta cell mass is the basic mechanism leading to diabetes mellitus. The ULB Center for Diabetes Research has discovered surface biomarkers specific for human beta cells and will use them to target novel therapies to protect and/or restore beta cells in diabetes. Targeting will be achieved by using novel viral vectors coupled to nanobodies directed to these surface biomarkers. These novel vectors will be validated in in vitro and in vivo (humanized mice) models. Interested applicants for the position should send a CV, a brief statement of their research interests, and contact information with three references to Dr. Decio Eizirik. 

Postdoctoral Position

Multiple Academia Postdoctoral positions for dry (computational), wet (experimental), or hybrid biologists are available in the lab of Dr. Golnaz Vahedi at the University of Pennsylvania. The Vahedi lab is multidisciplinary, integrating cutting-edge experimental and computational approaches to develop a mechanistic understanding of cell fate determination in the immune system. Interested applicants should submit a CV to Dr. Golnaz Vahedi.

Postdoctoral Position

The Imperial College London, under the direction of Dr. Dominguez-Villar, is recruiting a passionate and self-motivated postdoctoral research associate with expertise in the identification and characterization of antigen-specific T cells in humans.  The research programme led by Dr. Dominguez-Villar focuses on understanding the molecular mechanisms that maintain peripheral tolerance, with a particular focus on human regulatory T cell identity and plasticity and the regulation of CD4⁺ T cell responses in autoimmune and infectious disease settings. Interested Applicants for the position should send a CV, a brief statement of their research interests, and contact information with three references to Dr. Margarita Dominguez-Villar.

Postdoctoral Position

The Stitzel Lab at The Jackson Laboratory for Genomic Medicine in Farmington, CT is recruiting a Postdoctoral Associate to join their scientific team working to understand the precise genetic mechanisms controlling pancreatic islet identity and function and identify genes and response pathways that can be therapeutically targeted to prevent islet dysfunction and enhance islet resilience. Interested applicants for the position should send a CV, a brief statement of their research interests, and contact information with three references to Miriam Ortiz. 

Postdoctoral Position

The Arvan laboratory (University of Michigan) has availability for one postdoctoral trainee in the area of pancreatic beta cell biology of the secretory pathway. The primary focus of work in the Arvan lab centers around the genes and environmental factors controlling the biogenesis and storage of insulin secretory granules, and defects in such genes/factors that contribute to the development of beta cell failure in diabetes. It is expected that the successful postdoctoral candidate for this position would have recent PhD training in cell biology, biochemistry, molecular biology, physiology, or related field. For more information, contact Dr. Peter Arvan, Division of Metabolism, Endocrinology & Diabetes, University of Michigan, Dr. Peter Arvan.

Postdoctoral Position

The University of California, Los Angeles is seeking a highly motivated postdoctoral associate interested in the interface of diabetes research and molecular imaging. This highly translatable research seeks to leverage the non-destructive, whole-body, and quantitative power of molecular imaging to directly visualize host immune-mediated rejection of allogenic β-islet grafts. The candidate is expected to lead this research initiative and deliver on research milestones described in the collaborative research initiative funded by the Juvenile Diabetes Research Fund (JDRF). Candidates with experience in diabetes research interested in engaging in innovative molecular imaging or molecular imaging scientists excited to engage in research on the intersection of immunology and diabetes are strongly encouraged to apply. Interested candidates should provide a CV, cover letter, three references, and a summary of research experience to Dr. Oluwatayo Ikotun.