MIR LAB

Single molecule dynamics of gene expression and nuclear organization during embryonic development

Children's Hospital of Philadelphia and University of Pennsylvania

 

WHAT WE DO

We develop and apply new imaging technologies to understand and manipulate the interplay between nuclear organization and gene expression.

Video 1: 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 myriad mechanisms that are at play in regulating 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 2: 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 utilize high-resolution light-sheet microscopy methods which allows us to probe this vast range of spatial and temporal scales within living embryos (so far in Mice, Drosophila, and C. elegans). For example, we can acquire: high-speed volumetric data to quantify chromatin dynamics (Video 1), 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 2), 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 3). 

Video 3: Single molecule dynamic of a pioneer transcription factor (Zelda-green) as they bind 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

The goal of our lab is to comprehend and manipulate the interplay between nuclear organization, transcription regulation, and gene expression patterns during cell-fate determination in developing embryos. We use a combination of advanced imaging technology, biophysical modelling, genomics, and gene editing. We are also especially interested in the interactions between the disordered regions of proteins incorporated into various types of sub-nuclear assemblies and their role in nuclear organization. Additionally, we develop new microscopy technology that allows us to access a broad range of spatiotemporal scales, ranging from single molecule kinetics to patterning across entire embryos.

Our vision is to utilize quantitative data in combination with mechanistic modelling to develop new strategies to specifically manipulate nuclear organization and transcriptional regulation to achieve desired phenotypes. The insights gained through these projects will not only lead to an improved understanding of one of life’s fundamental processes, transcription, but will also be applicable to the plethora of diseases which have a basis in the misregulation of gene expression.

We are committed to doing bold, rigorous, open, and curiosity driven science. As a lab we strive to be communicative, empathetic, inclusive and kind.

Want more details? Get in touch!

JOIN US!

Do you love mind-blowing microscopy?

Are you interested in unveiling the molecular level details of how embryos are patterned?

 

Are you fascinated by disordered proteins?  

Do you want to help build a quantitative framework to describe

and manipulate  gene expression?  

We are building an interdisciplinary team of biologists, engineers, physicists, and computer scientists. Multiple positions are available:

Research Assistant/Technician

This position is currently filled but we are always interested in hearing from curious scientists!

Post-doctoral Fellows

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 (mirm@chop.edu) for more details!

 

Graduate Students

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.

Undergraduate Researcher

Interested in our research? Please email Mustafa (MIRM@email.chop.edu with your scientific interests, future career goals, any lab experience you have and courses you have taken.

GET IN TOUCH

The fastest way to get in touch is to email Mustafa at MIRM@chop.edu

Follow us on Twitter (@MustafaMir16)

The lab is located on the 9th floor of the Colket Translational Research Building