Sebastian Brauchi, Ph.D.

Research

The Biophysics Laboratory at Universidad Austral de Chile investigates cellular physiology through the lens molecular evolution of bioelectrical signals. We are focused in examining how transport systems—ion channels and receptors—localized at the cellular and intracellular membranes support homeostasis and enable cells to process environmental information via rapid modulation of bioelectrical signals. Our research employs diverse methodologies, including electrophysiology, advance imaging, molecular biology, protein engineering, and custom software development.

Each cell can be understood as a sophisticated molecular circuit that continuously detects environmental cues and generates coherent responses. To study this highly dynamic process, our research conceptualizes plasma membrane subspaces and the different organelles as individual information-processing nodes within a dynamic physical network, where each organelle contributes to cellular decision-making via metabolic control and inter-organellar communication. Currently, we are searching for overarching principles that enable cells to process information and respond consistently to recurring stimuli. This concept underpins much of biomedical and pharmacological research. Our experimental approach involves multiplexing elements of membrane physiology, including membrane voltage and ion flux monitoring, as well as organelle positioning, to map a subcellular signaling structure at the millisecond scale. We aim to generate unique hierarchical maps of subcellular functional connectivity. Combined with subcellular proteomics and contact site mapping, our goal is to decode the principles of cellular wiring, a general concept that remains conceptually vague. We are guided by key questions: whether organellar electrical activity correlates with subcellular organization, how contact site remodeling affects bioelectric signals in large cellular scale, whether subcellular topology of organellar arrangement correlates with distinct metabolic states, and whether some cellular programs are evolutionary conserved. This integrated approach seeks to establish foundational knowledge about cellular information processing and stress responses.

In the context of the Pew Innovation Fund, my laboratory will be in charge of the biophysical description of membrane and membrane protein properties, as well as contributing to the molecular evolution bioinformatic pipeline.

As an Innovation Fund investigator, Sebastian Brauchi, Ph.D., is teaming up with John Tuthill, Ph.D., to understand how snow flies continue to function in very cold temperatures. In subzero conditions, ion transport slows and protein movement decreases, jeopardizing the membrane potential and conduction of electrical signals, which are key for neuromuscular function. Yet, snow flies can still move at internal temperatures as low as -10 degrees Celsius. The team will test the hypothesis that snow flies have evolved specific proteins such as more flexible ion channels and pumps, thus allowing them to function at lower temperatures than other insects. The project combines the Tuthill lab’s expertise in insect neurobiology and behavior with the Brauchi lab’s extensive experience studying the biophysical properties of ion channels. Together, they will integrate in vivo electrophysiological recordings, protein sequence analysis, and first-of-their-kind measurements of membrane biophysical properties in subzero conditions to understand how insects have adapted to sustain movement in extreme cold. This work could spark broader investigation of the adaptations of diverse cold-active species.