Key questions within the biological and biomedical sciences require an understanding of complex dynamical systems. This includes physics approaches to modeling microbial communities. This talk will focus on microbial dynamics in the context of evolving ecosystems and disease. More specifically, the talk will present the role of the microbiome--the microbes that live in and on our bodies, working in concert with our human cells to promote health or to cause disease--in light of their distributional properties and ecological dynamics.
Inner-ear mechanotransduction is initiated when mechanical stimuli from sound and head movements stretch tip-link protein filaments to open ion channels that trigger sensory perception. These inner-ear mechanotransduction channels are formed by transmembrane channel-like (TMC) proteins 1 and 2 in complex with auxiliary subunits calcium and integrin- binding (CIB) proteins 2 and 3. Here, AlphaFold 2 models and nuclear magnetic resonance experiments reconcile previous biochemical evidence to suggest a 'clamp-like' interaction involving two cytosolic TMC1/2 domains and CIB2/3. Molecular dynamics simulations of these models provide additional insights into possible mechanisms underlying CIB function in mechanotransduction. Isothermal titration calorimetry experiments provide further information on binding affinities and Ca2+-dependency of CIB binding. Together, experiments and simulations provide insight about TMC:CIB interactions and suggest how the complex may function in inner- ear mechanotransduction.
Proteins typically carry out their biological function as parts of multimeric complexes. Recent advances in mass spectrometry (MS) have enabled the study of these complexes in their native form in the gas phase (nMS). nMS experiments can provide accurate molecular weight and stoichiometric information, while the study of structural characteristics can be performed using tandem MS with an activation step. Surface induced dissociation (SID) has emerged as an activation step for tandem MS that helps reveal the architecture of protein complexes. However, the SID process for large protein complexes is still not fully characterized at an atomistic level. In this study, we have used a well-characterized dimer formed by fragments of cadherin-23 and protocadherin-15 proteins essential for hearing as a model system to understand the atomistic behavior of proteins during SID. After first testing the interaction experimentally using nMS and SID, we then advanced to simulations of surface impacts to study energy transfer and potential dissociation. Using the simulations, we have been able to determine parameters affecting energy transfer. We plan to continue to better characterize the SID process to assist in experimental design.
Last update: 1/16/2024, Ralf Bundschuh