Seminar: Belinda S. Akpa, North Carolina State University
Title: "Realizing the potential of ‘tiny data’ – a cell biology case study."
Stomata are the pores on a leaf surface that regulate gas exchange. Each stoma consists of 2 guard cells whose movements regulate pore opening and thereby control CO2 fixation and water loss. Guard cell movements depend critically on the remodeling of cell vacuoles, which have been observed to change morphology from a highly fragmented state to a fused state during stomata opening. The evolution of vacuole morphology requires a membrane fusion mechanism that responds rapidly to environmental signals, allowing plants to respond to diurnal cues or environmental stresses such as drought. With guard cells being both large and responsive to external signals, stomata represent a unique system in which to delineate mechanisms of membrane fusion and fission.
To resolve a counter-intuitive observation regarding the role of the HOPS protein complex in regulating vacuole morphology, they derived a quantitative model of vacuole fusion dynamics and used it to generate testable predictions about HOPS-SNARE interactions. They derived their model from limited - and, initially, qualitative - data by integrating statistical inference with fluorescence imaging and mechanistic modeling. The dynamic model predicted the evolution of vacuole morphology as it arises from intracellular signaling events that include: cytosol-to-membrane recruitment, chaperoned protein complexation, and complex disassembly.
By constraining the model parameters to yield the emergent outcomes observed for stoma opening (as induced by two distinct signals), they predicted a dual role for HOPS and identified a stalled form of the SNARE complex that differs from phenomena reported in yeast. They predict that HOPS has apparently contradictory actions at different points in the fusion signaling pathway, promoting the formation of SNARE complexes, but limiting their activity. By using their multiscale model to predict how genetic mutations might impact the rate of vacuole remodeling, they have crafted a targeted experimental strategy that will ultimately yield a predictive model for re-engineering stomata opening and improving plant fitness.
Belinda S. Akpa is an Assistant Professor of Integrated Synthetic and Systems Biology at North Carolina State University (NCSU). She holds a BA, MEng, and doctorate in Chemical Engineering from the University of Cambridge (UK). A highly interdisciplinary researcher, her current interest is in developing mathematical frameworks that integrate scarce and heterogeneous data to connect molecular phenomena to dynamic physiological outcomes. Akpa is broadly interested in mathematical biology, but more specifically in how mechanistic mathematical models can be used to inform targeted experimental strategies. By necessity, these efforts explore the limits of what one can learn from empirical observations and mathematical models, both independently and in integrative studies.
Akpa joined NCSU after serving on the faculty in the Department of Chemical Engineering at the University of Illinois at Chicago (UIC), where she initiated her interdisciplinary research program in systems physiology. Her work has been published in chemistry, interface science, pharmaceutical, and clinical journals. She has mentored graduate and undergraduate research students with academic backgrounds ranging from chemical engineering and biology to pharmacy and astronomy. She is also the recipient of the Harold Simon Award, UIC College of Engineering’s highest teaching distinction.
Tuesday, December 3, 2019 at 3:30pm to 4:30pm
Dougherty Engineering Building, 416
1512 Middle Drive, Knoxville, TN 37996