Our lab uses state-of-the-art fluorescence microscopy to understand how genes are turned on and off in living cells and organisms. We hope to someday control this process and thereby correct gene misregulation in diseases like cancer.
To deconstruct gene regulatory dynamics, we have developed techniques to image and quantify the kinetics of the central dogma of molecular biology with single-molecule precision in living cells.
Capturing translation dynamics live, one molecule at a time
Despite the fundamental role of translation in gene expression, our understanding of the process has been limited by the low spatio-temporal resolution of traditional experimental techniques. To address this issue, my lab has helped pioneer live-cell imaging of single-mRNA translation dynamics. Our goal is to create open technology to decipher translational regulation and better understand its misregulation in human disease.
Capturing transcription dynamics, straight from the source
A remarkable finding from live-cell imaging is that transcription occurs in distinct bursts. Our work is trying to understand the origin of these bursts. Using a combination of antibody-based probes, amplification tags, genome editing, and single-molecule microscopy, we are capturing the dynamics of the transcription cycle with unprecedented spatiotemporal resolution.
Lighting up endogenous protein modifications in vivo
Most studies of protein modifications are performed in bulk or rely on fixation, both of which limit temporal resolution and wash out single-gene heterogeneity. This makes it difficult to track dynamic changes to protein modifications and assess their impact on gene regulation. To confront this problem, we use antibody-based probes to light up the modifications live, focusing mainly on how histone modifications help turn genes on and off.
Engineering antibodies for live-cell imaging
To image the full protein life-cycle, we engineer designer antibody-based probes for live-cell imaging. Typically antibodies do not fold well in the reduced environment inside cells. To overcome this, we combine rational design with machine-learning and AI. This creates stable probes that can be expressed from plasmids and that can bind and light up endogenous nascent proteins, conformational changes, and post-translational modifications.
Primer on our technology to image translation:
About CSU: Colorado State University is a land-grant institution encompassing 57 academic departments in eight colleges with over 33,000 students. The University is located in Fort Collins, a (beer, bike, music, and dog!) friendly city of 161,000 located at the foot of the Rocky Mountains. The campus is an hour’s drive from Rocky Mountain National Park and has ready access to thousands of square miles of forest and mountains with exceptional outdoor recreational opportunities, including skiing, hiking, mountain biking, and rock-climbing. Fort Collins has an excellent school system, an impressive selection of restaurants and quality fine arts programs, and the resources of Denver are just an hour’s drive away.
How to apply: Please send a C.V., cover letter, and contact information for three professional references to: tim.stasevich@colostate.edu.
The Stasevich lab is located in the Department of Biochemistry and Molecular Biologyat Colorado State University in lovely Fort Collins . If you have any questions or are interested in visiting or even joining the lab, please don't hesitate to contact us! We currently have open post-doctoral positions!
