Children's Hospital of Philadelphia and University of Pennsylvania
Molecular kinetics of gene expression and nuclear organization during development and in disease
WHAT WE DO
We quantify and manipulate the dynamics of nuclear organization and gene expression during development and in disease. To do so we build and apply advanced light microscopy technologies alongside computational analysis, biophysical modelling, optogenetics, gene editing, and genomics.
Video 1: Construction of our MOSAIC Adaptive-Optics Light-Sheet Microscope
Video 2: Mitosis in a syncytial Drosophila embryo (H2B)
Gene expression is regulated by a complex choreography of highly dynamic events, including the binding of transcription factors to non-coding regulatory regions of the genome, regulation of chromatin topology, and the assembly of large macromolecular complexes, all of which occur in the crowded nuclear environment.
Our understanding of these dynamic processes has largely been driven by approaches that provide population averaged and static snapshots which have delivered remarkable insights, but are inherently ill suited for elucidating processes that vary greatly in space and time.
Comprehending the mechanisms that regulate gene expression, and the role of nuclear organization in this regulation, requires technological and theoretical approaches that bridge spatial scales from molecular to organismal and temporal scales from milliseconds to days.
Video 3: Proteins associated with gene activation (GAF-green) and repression (HP1-magenta) in a Drosophila embryo.
(In collaboration with Harrison lab at U. Wisconsin)
We develop and use high-resolution microscopy methods which allow us to probe this vast range of spatial and temporal scales within living embryos, tissue slices, and single cells. For example, we acquire: high-speed volumetric data to quantify chromatin dynamics (Video 2), multi-color datasets to study the interaction and distribution of protein domains associated with gene activation or repression as cell fates are determined in young embryos (Video 3), and use single molecule localization techniques to quantify the kinetics of individual transcription factors as they whizz around the nucleoplasm searching for and binding to their genomic targets (Video 4).
Video 4: Single molecule dynamics of a pioneer transcription factor (Zelda-green) as it binds chromatin (H2B-red) in a Drosophila embryo. The edge of the embryo is visible as a bright red line on the right of the video
Do you love mind-blowing microscopy?
Are you fascinated by the molecular mechanisms of transcription regulation and embryonic development?
Are you crazy about disordered proteins?
Do you want to help build a quantitative framework to describe
and manipulate gene expression?
We are an interdisciplinary team of biologists, engineers, physicists, and computer scientists. See below for available positions:
This position is currently filled.
Our research is highly interdisciplinary and as such we are open to postdocs from a variety of backgrounds.
We have opportunities to apply advanced microscopy methods to study transcription regulation and nuclear organization in developing embryos / develop new advanced microscopy / develop new ways to analyze large imaging datasets / combinations of the above and more!
Please email Mustafa (firstname.lastname@example.org) for more details!
Any graduate student at Penn is welcome. Within BGS we are a member of BMB and DSRB, we are also a part of the Bioengineering graduate program. Please email Mustafa (mirm@.chop.edu) to set up a time to meet and visit the lab.