CAREER: Studying Weak Interactions in Biological Systems, Forming Strong Interactions Between Students

University Of Minnesota Duluth, Duluth MN

Investigators

Abstract

For the delivery of signaling molecules in a cell to occur, the membranes of the vesicle in which signaling molecules are packaged must fuse with another membrane. As timing is vital in cellular processes, this delivery of signaling molecules must be poised to trigger only when the appropriate signal or combinations of cellular signals transpire. Although this is a critical cellular event, how this regulated delivery occurs is not well understood. Membranes are comprised of a great diversity of lipids whose individual lipid-lipid interactions are weak and interactions within the membrane dictated by the lipids' chemical structure and its local milieu. These factors govern the resultant lipid's activity (effective concentration) and hence, how the membrane is targeted for binding to or partitioning into by proteins. Within this model, it is hypothesized that intrinsically weak interactions between lipids are critical for the system to reversibly and rapidly organize the protein clusters that modulate signaling. This offers a more nuanced regulation of biological events beyond a system dominated by a few, very strong interactions. These small interaction energies offer flexibility in how combinations of lipids, in response to proteins binding, form signaling platforms. This concept is hypothesized to be the basis for how key proteins involved in regulated delivery target distinct membranes. The objective of this project is to test the hypothesis that these key proteins are modulated not by a few strong interactions but by a necessary ensemble of weak interactions at the membrane. Testing will involve quantitative analysis and rigorous use of binding theory and thermodynamic (linkage) relationships by undergraduates from diverse scientific disciplines. New techniques, both conceptual and experimental, will also result from this project that will be applicable to many questions of biological relevance. The classic use of linkage relationships is an example of problem-based learning where biological processes are simply represented mathematically and interpreted. Each experiment becomes a case study and the derivation of equations is no longer restricted to assigned homework or to be used after years of graduate training. The goal is to demonstrate that undergraduates and young graduate students can propose, use, explore, and test these concepts. Broader Impacts The Broader Impacts of this project include the development of methodologies that will enhance the persistence, retention, and future success of women in scientific careers. By improving the educational environment for women, the educational environment not only for underrepresented groups but for all students will be improved. The methodologies will have two components, Informal and Formal Education. The Informal structure for this change is a scientific council, named Interactions. This council will integrate all issues that are faced by future science, mathematics and engineering (SME) professionals. Potential topics will include: social dynamics (e.g. bias), the importance of building a community in addition to a resume (or CV), the need to apply for research scholarships, academic scholarships and awards, and how these experiences can shape your future. Interactions will provide in-house educational meetings and host motivating role models such as distinguished female scientists, alumni, and scientists from the region who have gone on to illustrious careers. Interactions will also foster peer group learning. The existence of peer group learning has been identified by SME students as having the most immediate and most effective contribution to increasing persistence of students within SME majors. The Formal component is a Physical Biochemistry capstone course with laboratory capturing the convergence of topics across the major and explicitly uniting concepts through application. The linkage of biochemistry with other disciplines will be through quantitative literacy where the grammar is Physical Chemistry. A course focused upon practical outcomes will emphasize female specific advantages in learning as it is argued that many other learning strategies are inherently favorable to male learning patterns. Gender differences in learning strategies will be equalized through multiple approaches to problem solving, and the commonalities between seemingly diverse topics will be emphasized.