SPUR 2021: Immune and metabolic cell cross-talk in autoimmune diabetes

Background

Type 1 Diabetes (T1D) is an autoimmune disease that precipitates as a result of destruction of insulin producing beta cells by the rogue cells of the immune system. This leads to dysregulation of glucose metabolism leading to negative effects on multiple systems and disease associated complications. There is no cure for T1D. Our laboratory is investigating the interactions, both direct and indirect, between T cells and beta cells. T cells can target beta cells for destruction, but there also exists an anti-inflammatory subpopulation of T cells that can prevent or reverse autoimmunity – regulatory T cells. Regulatory T cells are currently tested in multiple clinical trials as a therapy for autoimmune diseases and transplant tolerance, but we still do not have complete understanding of their functional potential and molecular mechanisms. What is exciting, is that several molecules produced by regulatory T cells can signal directly to beta cells and potentially improve their survival under inflammatory conditions. Current work in the lab is further dissecting these signals using mouse models of T1D, flow cytometry, microscopy, and single cell genomics. We are also interested in how T cells themselves are affected by diabetes, and how they respond to changing metabolic conditions.

Student Role

For this project, the student will work with the faculty mentor and a graduate student to develop an abstract of the proposed summer project based on the ongoing study in the lab. This will be accomplished by discussions with the faculty mentor, the graduate student, and integration of the assigned reading material. The objective is to outline a research goal that fits within the ongoing study, can be realistically completed within the allocated time, and have an important contribution to the work with a potential for authorship on a manuscript. The study should fit within the scope of the current project spearheaded by the graduate student mentor. The student will then work with the graduate student mentor to implement the proposed study. The student will learn and use techniques such as cell culture, flow cytometry, and microscopy to study T cell function and beta cell survival in a mouse model of diabetes. The student will receive training in sterile cell culture techniques, introduction to flow cytometric analysis of immune cells, and tissue staining and confocal microscopy of the autoimmune pancreas. It is expected that by the end of the program the student will have both theoretical knowledge of the subject and experience in one or two practical approaches to address scientific questions in immunology and metabolism..

Student Learning Outcomes & Benefits

The objectives of the training are threefold:

  1. develop theoretical understanding of the project from reading assigned material, weekly meetings with the faculty mentor and the graduate student mentor, attendance at weekly laboratory meetings, and independent study;
  2. acquire technical proficiency in appropriate immunological assays under the mentorship of the graduate student;
  3. cultivate presentation skills by discussing experimental results with the faculty member, and presenting the results of the study to the rest of the research group at the completion of the project.

The student will work closely with the graduate student mentor to learn new techniques and assays, but will also be encouraged to gain independence in their role in the project. Students will also be able to attend lab meetings and seminars to further their knowledge in other aspects of immunology, but also in broader scientific fields. This will allow the student to develop their presentation skills, laying the groundwork for future speaking engagements. Furthermore, as the lab is currently a robust research environment, the student will be given opportunities to engage with other lab members and learn about other ongoing projects in the lab. This will allow the student to develop an appreciation for a variety of scientific topics.

Remote Contingency Plan

In the case that SPUR work has to be done remotely, the project will be modified to focus on gaining skills in reading, understanding, interrogating, and writing primary research manuscripts. Through this process, the student will make contributions to a research manuscript on the topic of regulatory T cell function and metabolism. To accomplish this, the student will be assigned background reading on the topic, followed by guided independent research into a specific concept to be covered in the manuscript. Under the guidance and mentorship provided by the faculty member and the graduate student, the student will develop a written contribution to the manuscript by investigating a specific concept or question. This will become a section in a primary literature review manuscript or a section in the discussion of the primary research article. In addition, the student will provide comments to the manuscript draft as a whole. The student will meet at least on a by-weekly basis with the faculty and the graduate student mentor via Zoom, attend weekly Zoom lab meetings, and attend Zoom Department seminars. The primary objectives of this experience are to obtain skills in reading, understanding, and critical evaluation of primary research literature. The student will have an opportunity to contribute and become a co-author on a manuscript. At the end of the training period, the student will present the findings from the research and outline potential future directions in the area of investigation.

Maria Bettini
Associate Professor

Pathology
School of Medicine

My training philosophy is guided by emphasis on tangible accomplishments that promote student learning and career development. We start by identifying specific goals, followed by developing step-by-step activities to achieve these goals (i.e. starting by first writing an abstract). I believe this structured approach to scientific career building has allowed my trainees to reach their objectives in record amount of time. For example, my first graduate student graduated under five years with seven publications, on four of which she was the first author. In my experience, undergraduate research can be an exciting first exposure to the scientific method. Most of the undergraduates that I have trained have fun and engaging experiences in the lab, and that can be easily achieved in a lab with a collegial atmosphere. However, tangible accomplishments can be challenging for undergraduate trainees due to their limited time in the lab. Therefore, our approach is to create a structured environment built on early planning and weekly scheduled interactions to ensure the best path for success. We will develop a research plan guided by pre-determined assigned reading based on already ongoing projects. In parallel to learning experimental techniques in the lab, the student will have continuous mentorship to achieve a step-wise progress in generating a poster and a power point presentation, since the two activities have a large degree of overlap. We will achieve this through using examples, templates from the lab, and several iterations of the drafts based on our discussions in our weekly meetings.