26 June 2015
John Albeck
Departments of Molecular and Cellular Biology
UC Davis
As single-cell technologies expand, it is becoming clear that many cellular signaling events are very dynamic, necessitating a time-lapse approach. I will present our work on the single-cell kinetics of two kinases – ERK and AMPK – that integrate growth signals and metabolism to control cellular proliferation and homeostasis. For both of these kinases, we have found that different natural and pharmacological perturbations result in distinct kinetics that cannot be detected by population-level assays such as immunoblots. In both cases, we observe highly dynamic responses that persist for days following the stimulus. Together these findings underscore the concept that, despite the chemically specific nature of modern targeted cancer therapies, their usefulness may be limited by the highly variable kinetics that they induce within cellular populations, resulting in sub-optimal, heterogeneous responses. We are currently working to decode the cellular "meaning" of these dynamic signal patterns in terms of gene expression, cell cycle progression, and apoptosis.