May 2024

NEWSLETTER

IDENTIFYING THE TARGETS OF AUTOIMMUNE ATTACK IN TYPE 1 DIABETES

CD4+ T cells are well known for their role in mediating the destruction of pancreatic beta cells. A key feature of autoimmune T cells is their antigenic specificity, which is conferred by their surface T cell receptor (TCR). TCRs from CD4+ T cells recognize peptide epitopes presented in class II MHC molecules, and thereby invoke a functional response by the T cells. While it is well known that CD4+ T cells that infiltrated the pancreatic islets are likely specific to islet autoantigens, the overall landscape of their recognition is not well understood. A significant contributing factor to this lack of knowledge is the availability of robust methods for CD4+ T cell antigen discovery. A recent paper by the Joglekar laboratory at the University of Pittsburgh has developed a cell-based antigen discovery method that relies on receptors known as Signaling and Antigen-presenting Bifunctional Receptors (SABRs). Expanding upon their previously published use of SABRs for class I MHC, here, the Joglekar lab has deployed SABRs for class II MHC, allowing profiling of autoreactive T cells. Using this method, they have built antigen libraries that are designed to specifically present b cell proteins, including Hybrid Insulin Peptides (HIPs). Here, the researchers have applied these libraries to uncover the antigenic landscape of islet-infiltrating CD4+ T cells in NOD mice, and extended the approach for human antigen discovery. Furthermore, the researchers have integrated computational TCR deconvolution methods to enhance antigen discovery. These methods will allow Type 1 Diabetes researchers to understand how T cells target beta cells specifically, to create novel diagnostic tools to study autoimmunity, and to identify therapeutically targetable antigens.

Manuscript Information:

“De novo identification of CD4+ T cell epitopes”. Zdinak PM, Trivedi N, Grebinoski S, Torrey J, Zarate Martinez E, Martinez S, Hicks L, Ranjan R, Makani VKK, Roland MM, Kublo L, Arshad S, Anderson MS, Vignali DAA, Joglekar AV. Nature Methods. 2024 Apr 24. PMID: 38658646.

TIPS FOR THE NIH DATA SHARING MANDATE

Reoccurring Series

Tip #10:  How to Request and Access Datasets from dbGaP 

Many NIH repositories with controlled-access human genomic data require that users request access to datasets for research projects through dbGaP. NIH requires anyone interested in using controlled-access genomic data to meet minimum qualifications and to apply for access to the data. If the request is approved, the investigator will be allowed to access the dataset for one year, with the option to renew. Those eligible to apply must be a permanent employee at their institution and are required to be at a level equivalent to a tenure-track professor, or a senior scientist with responsibilities that may include laboratory or research program administration and oversight. Once an application has been submitted and approved through a detailed review process by the NIH, investigators will receive an email with detailed instructions on how to access the data. Investigators and their institutions are responsible for safeguarding the accessed datasets.  

Click HERE to access the step-by-step breakdown of the data access and request process out forth by the NIH  

UPCOMING MEETINGS

The NIDDK is holding a virtual Diabetes Mellitus Interagency Coordinating Committee (DMICC) meeting on “Artificial Intelligence in Diabetes Precision Medicine: Real World Data, Real World Opportunities and Challenges” on Thursday, May 30, 2024, from 12:00-3:00 PM EST. It is organized in recognition of the recent rapid advancement in Artificial Intelligence (AI), and the significant gains made in AI that have the promise and potential to significantly improve diabetes management, reduce complications and potentially reduce cost of care. Presenters and panelists are experts and leading researchers in AI and in precision medicine of diabetes and other chronic conditions, representing federal agencies, industry and non-profit organizations. Together they will discuss the current status, gaps, challenges and opportunities.



Additionally, NIDDK is planning an in person workshop, on October 30-31, 2024, Bethesda MD, entitled “AI in Precision Medicine for Diabetes and Other Chronic Diseases: Challenges and Opportunities in Developing Predictive AI Models and Biomarkers for Disease Initiation, Progression, Prevention, and Subtypes”. This workshop aims to bring together biomedical researchers and data science/AI experts, to discuss the critical challenges, crosscutting gaps, and opportunities and actionable items in leveraging AI and other recent data science advances in precision medicine. For more information click HERE.

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 one of the new nPOD working groups, please visit our website to learn more and sign up to participate.

Contact nPOD to join them 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

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.

Postdoctoral Position

The Thurmond Lab in the Arthur Riggs Diabetes & Metabolism Research Institute, within the Beckman Research Institute of City of Hope, is looking for a highly motivated and team-science minded Postdoctoral Fellow, to study the molecular mechanisms involved in regulating functional beta cell mass, skeletal muscle insulin action, whole body glucose homeostasis, and healthspan/lifespan. The lab specializes in detailed studies of signaling/trafficking/exocytosis, using primary human and rodent islet cells, skeletal muscle cells and adipocytes. Interested applicants please send a cover letter and curriculum vitae, including the names of three references, to Dr. Debbie Thurmond.

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

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.