CBE 298 Seminar (Zoom): Molecular Investigations Of Protein Interactions And Membrane Dynamics

Zoom Link: Please contact Professor Herdeline Ardona (hardona@uci.edu).

Abstract: We consider the impact of molecular study of two pathophysiological conditions. Dyslipidemia (elevated blood levels of low-density lipoproteins (LDL)) is a major risk factor for the development of cardiovascular disease, however, the impact of LDL on membrane cholesterol levels, structure and function remains poorly understood. Cells exposed to elevated concentrations of circulating lipoproteins experience a subtle membrane increase in the levels of cholesterol and 7-ketocholesterol, as compared to normal conditions. Charcot-Marie-Tooth (CMT) disease is a progressive neurological disorder associated with disruptions in the myelin sheath that inhibit the motion and control of the peripheral limbs. Amino acid substitutions of Myelin Protein Zero (MPZ), the most prevalent protein found in the myelin sheath, have been identified in patients with this disorder, however, the effects of these mutations are unclear.

In our studies, we use experimental and computational methods to investigate the effects of MPZ mutations on protein interactions and dyslipidemic conditions on multicomponent model bilayer membranes. We find that significant changes in the structural and dynamic properties of bilayer membranes result from subtle increases in sterol levels. We also observe that, although there have been over 200 potential point mutation sites identified in CMT patients, the test case of an alanine substitution in the extracellular region of MPZ results in perturbed interactions between MPZ molecules and a disruption of the intraperiod line distance between bilayer membranes. The results from these two studies indicate that the subtle increases in membrane sterol levels induced by exposure to lipoproteins result in molecular-scale biophysical perturbation of membrane structure and furthermore, bilayer membrane intraperiod line disruption could result in loss of neural signal, thereby impacting motor control downstream.

Bio: Manuela Ayee-Leong serves as an associate professor of Chemical Engineering at Dordt University, a primarily undergraduate institution in northwest Iowa. She obtained her baccalaureate at Dordt and earned her M.S. and Ph.D. in chemical engineering from Iowa State University and the University of Illinois at Chicago (UIC), respectively. After an NIH Pulmonary and Critical Care Postdoctoral Fellowship in the Department of Medicine at UIC, she began her faculty position at Dordt. Her research involves the use computational and experimental methods to elucidate molecular mechanisms underlying membrane modulation in pathophysiological contexts. Specifically, she probes the effects of small molecules and proteins on membrane biomechanics and cell biophysical properties using protein docking and molecular dynamics simulations. Some applications include examining: myelin protein zero molecular interactions to uncover mechanisms driving a peripheral neuropathy disease; oxidized lipid and sterol modulation of cellular and tissue biomechanics in hypercholesterolemic conditions; roles played by toxins in modulating properties of lipid layers.

In addition to research and teaching, Ayee-Leong has a significant interest in supporting students from traditionally underrepresented groups in STEM by facilitating initiatives to ensure their academic success. Consequently, she actively works to foster an educational environment where the recruitment and retention of academically talented students from traditionally underrepresented groups, first generation and lower income communities is prioritized. One such initiative is the NSF-funded S-STEM “RU-STEM Scholars Program,” administered by Ayee-Leong (PI), which awards annual tuition scholarships and uses evidence-based practices to foster academic success and build STEM identity among cohorts of scholars. She also serves as the faculty sponsor of the Women in Science and Engineering club on campus. Ayee-Leong is a senior member of the American Institute of Chemical Engineers (AIChE), an Officer of the Minority Affairs Community (MAC) at AIChE and an elected Trustee of the CACHE Corporation, which promotes the development and distribution of computer-related and technology-based educational aids for the Chemical Engineering profession.