Brehm Coalition Research

There is extensive research underway around the world in three main areas relating to type 1 diabetes -- beta cells, T-cells, and Tregs.

• Beta cells make and release insulin, a hormone that controls the level of glucose in the blood.
• T-cells belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity.
• Regulatory T cells (sometimes known as suppressor T cells) are a specialized subpopulation of T cells that act to suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self-antigens.

Instead of focusing on one area, the Brehm Coalition scientists are working on novel, multi-year scientific goals that are broken down into smaller collaborative projects between the immunologists and beta cell biologists.

1. Band the Coalition PIs together to explore dual (or multiple) pathways combining immunology and beta cell biology, addressing multiple factors, in a closely collaborative manner, as though in one lab.
2. Immunology Pathways focusing on:
   1. Eliminating or conditioning T-Cells that mount the autoimmune attack on the beta cells through development of a vaccine
   2. Designing a Treg cell that can moderate the actions of the T-Cells
3. Beta Cell Biology focusing on:
   1. Finding factors that promote beta cell differentiation and survival.
   2. Discovering reasons for failure of the cells as well as ways to cause precursor cells to differentiate into beta-like cells that produce insulin.
   3. Seeking to derive beta cells from clonal precursors as well as beta cells that may be regenerating in the pancreas after genetic or physiological suppression.
4. Structure the Pathways enough to monitor but not so rigidly as to be dominated by a single thread.
5. Foster side studies by associates to explore the boundaries.
6. Target a combination therapy solution that could be both safer and earlier.

To help accelerate the pace of discovery in type 1 diabetes research, the Brehm Coalition employs systems analysis and operations research. These are techniques designed to deal with the analysis of large, complex systems and the interactions among those systems. The analysts began by addressing key strategic and tactical tasks.

Strategic Tasks

• Characterize the universe of research in type 1 diabetes and establish a comprehensive picture of the research and resource landscape to leverage resources and accelerate research
• Identify barriers along the research continuum from basic research to therapies and determine if any of the barriers can be lowered or eliminated using a new approach
• Characterize the type 1 diabetes research enterprise and its current and potential participants, to assess how the elements fit and work together and to determine how they could be brought together in more productive ways

Tactical Tasks

• Identify opportunities for the coalition members to collaborate on scientific research
• Identify resources at the coalition member institutions that can be shared to reduce redundant expenditures of effort or money
• Identify organizations with potential to become collaborators and/or supporters of the work of the coalition to enhance shared missions

By understanding the strategic and tactical components of the type 1 diabetes enterprise, the members of the coalition can better:

• Optimize organization
• Prioritize research activities
• Understand beneficial partnerships
• Determine how to measure progress
• Break down barriers

Research

The Brehm Coalition’s research plan focuses on novel, multi-year scientific goals that are broken down into smaller collaborative projects distributed among the principal investigators and their colleagues. In many cases, the principal investigators are dependent upon each other owing to how they share the research effort and results.

Community Technology

Tight collaboration requires frequent discussions and the sharing of scientific information. The Brehm Coalition holds quarterly science review meetings, not via the frequent use of airline terminals, but through the frequent use of teleconferencing, operating from their own offices. They augment their virtual science exchanges with annual face-to-face conferences.
 

Analysis

The Brehm Coalition employs the discipline of high-level systems analysis to plan their work and to understand the enterprise of which the research effort is a part. This is a discovery process in its own right, as it reveals specific barriers to science and the development of therapies, thereby allowing the development of means to overcome or mitigate those barriers.

Infrastructure

A robust and diverse infrastructure supports the Brehm Coalition’s work with analysis, information science, and core capabilities - one that combines the strengths of several institutions.

Guiding Principles

The Brehm Coalition believes in a simple approach to guide their research and collaboration:

1. Self-organizing style not compromised by a rigid management approach imposed by others.
2. Unprecedented collaboration facilitated by frequent video conferences involving all Coalition members.
3. Respect for and trust in each other.
4. Dependence on each other for results.
5. Cooperation on, and even performance of, one another's experiments.
6. Sharing of institutional cores and other resources.
7. Enjoying each others' company - i.e., "fun to work with."