G. Edward Marti, Ph.D.
Molecular and Cellular Physiology
Stanford University, CA
IN-PERSON ONLY EVENT
The seminar will take place in the McDonnell Sciences Building, Room 423.
“New transcriptomic and imaging tools to track trajectories of aging and disease”
Abstract: We are in a biological imaging and measurement revolution as tools are rapidly advancing our ability to measure proteins at the nanometer-scale, cells at the micron-scale, tissues at the millimeter-scale and beyond. There is an unmet need to improve longitudinal measurements of molecular and cellular changes inside living animals and witness key events in an organism’s response to aging and disease progression. I will present our efforts to study changes in cellular heterogeneity in aging mice with single-cell transcriptomics, and to enhance the time resolution of single-molecule experiments with novel imaging techniques.
Single-cell transcriptomic atlases are teaching us that a “cell type” is really a heterogenous mixture of cells with a continuum of expression, yet it has long been contested how, or if, that heterogeneity changes with age. We developed a quantitative model of the measurement process from which we can identify genes with changing levels of biological noise from young adult to elderly mice. We find that genes involved in metabolism (specifically, oxidative phosphorylation) shows a ubiquitous decrease in noise and heterogeneity with age across disparate cell types and tissues.
Super-resolution imaging of bright nanoparticles enables us to track individual dynein molecular motors with a resolution of several nanometers and milliseconds. We are constructing a next-generation microscope towards angstrom localization in tens of microseconds to resolve record-fast dynamics of individual molecular motors and proteins. Furthermore, we are building a multimolecular platform with targeted microbubbles to image cellular changes by centimeters inside a living animal for days or weeks using ultrasound imaging.