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Mir Lab

@mirlab.bsky.social

650 followers 270 following 29 posts

Lab run by Mustafa Mir studying transcription and nuclear organization using live imaging at University of Pennsylvania, Children's Hospital of Philadelphia, and Howard Hughes Medical Institute. mir-lab.com

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Reposted by Mir Lab

Apratim (Appy) Mukherjee @mukherja.bsky.social · 20d

Huge props to our grad student @manyakapoor.bsky.social for developing the simulations and the new MS2 analysis amongst other things! We also thank the transcription community for their invaluable feedback and always welcome further discussion😊

Reposted by Mir Lab

Andrew Modzelewski @themodzlab.bsky.social · May 13

WE ARE HIRING! The lab got the Packard AND an R35! Please spread this PostDoc Ad around! Philly and Upenn are a great place to live and work!

Mir Lab @mirlab.bsky.social · Apr 11

5/n: Please reach out directly to me if you are interested. This is a unique opportunity at a time where increased centralized resources are critical to maintain and accelerate the pace of scientific discovery.

Mir Lab @mirlab.bsky.social · Apr 11

4/n We are seeking a microscope specialist/engineer. The role will include developing and implementing new microscope hardware, control software, customized analysis pipelines as well as collaborating with core users.

Mir Lab @mirlab.bsky.social · Apr 11

3/n We will provide custom built ad hoc optical microscopy solutions, advanced image analysis, and consultation services to researchers across campus and beyond. We will implement technology in response to experimental needs instead of working within the bounds of commercially available technology.

Advanced Core for Microscope Engineering (ACME) | Advanced Core for Microscope Engineering | Perelman School of Medicine at the University of Pennsylvania

www.med.upenn.edu

Mir Lab @mirlab.bsky.social · Apr 11

2/n: ACME is co-directed by myself (Mustafa Mir), Melike Lakadamyali @melikel.bsky.social (www.lakadamyali-lab.com), Yihui Shen (www.imaging-systems-metabolism-lab.com), and Andrea Stout @aleestoutphd.bsky.social (www.med.upenn.edu/cdbmicroscopycore)

Mir Lab @mirlab.bsky.social · Apr 11

1/n We have an exciting new initiative at UPenn to provide custom advanced microscopy solutions: Advanced Core for Microscope Engineering (ACME): www.med.upenn.edu/cdbacme/ We are looking for a specialist to help run this new facility, job description is attached please help share widely!

Mir Lab @mirlab.bsky.social · Apr 9

9/ We welcome feedback, questions, and critical discussion from the community. Huge thanks to all our amazing co-authors for their insight, support, and collaboration throughout this work.

Mir Lab @mirlab.bsky.social · Apr 9

8/n: We suggest that enhancers encode the biophysical properties of transcription factor hubs (intensity and stability) through binding affinities and cofactors. Hub properties dictate gene occupancy and transcriptional kinetics, suggesting hubs are active executors of enhancer-encoded regulation.

Mir Lab @mirlab.bsky.social · Apr 9

7/n: Hub intensity and duration correlate with burst amplitude, loading rate, and output suggesting that persistently interacting hubs with more molecules tune gene expression. Consistent with the idea that hubs facilitate transcription factor binding and promote expression.

Mir Lab @mirlab.bsky.social · Apr 9

6/n: Hub presence at a gene is correlated with increased transcription burst amplitude, Pol II loading rate, and total output. Surprisingly, transient interactions between Dorsal hubs and hunchback (lacking Dorsal binding) boosts transcription in ventral nuclei where Dorsal concentration is highest

Mir Lab @mirlab.bsky.social · Apr 9

5/n: We found:
• snail has persistent hub interactions with high-intensity hubs
• sog: has slightly less persistent hub interactions with lower-intensity hubs
• hunchback (negative control): transient interactions without stable hub formation

Mir Lab @mirlab.bsky.social · Apr 9

4/n: Next we examined Dorsal hub interactions at two target genes with distinct Dorsal occupancy and enhancer grammars, snai and sog, and as a negative control examined hunchback which has no dorsal sites.

Mir Lab @mirlab.bsky.social · Apr 9

3/n: First, we find that hubs form rapidly after mitosis and last through interphase. Nuclear hub density doesn't depend on nuclear concentration but hub intensity does, suggesting that hub formation may be independent of concentration, but hubs accumulate more protein with increased concentrations.

Mir Lab @mirlab.bsky.social · Apr 9

2/n: Transcription factor hubs (dense local accumulations) regulate gene expression by promoting the frequency of binding. They are often discussed as having uniform properties based on protein sequence and concentration. We wondered if their biophysical properties vary in a gene dependent manner.

Mir Lab @mirlab.bsky.social · Apr 9

1/n: Excited to share our new preprint. We find that Dorsal transcription factor hubs exhibit gene-specific biophysical properties that tune transcriptional output. Read here: www.biorxiv.org/content/10.1.... Project was led by amazing graduate student Samantha Fallacaro (not on bsky)

Transcription factor hubs exhibit gene-specific properties that tune expression

The spatial and temporal control of gene expression relies on transcription factors binding to and occupying their target sites. Transcription factor hubs - localized, high-concentration microenvironm...

www.biorxiv.org

Reposted by Mir Lab

Nadine Vastenhouw @nvastenhouw.bsky.social · Mar 28

Martino Ugolini and I wrote a review on how useful embryos are to understand the role of transcription bodies in gene expression. I am sure
@mirlab.bsky.social, @harrisonflylab.bsky.social, @lennarthilbert.bsky.social and others would agree. Enjoy the read! portlandpress.com/biochemsoctr....

The role of transcription bodies in gene expression: what embryos teach us

Transcription does not occur diffusely throughout the nucleus but is concentrated in specific areas. Areas of accumulated transcriptional machinery have been called clusters, hubs, or condensates, whi...

portlandpress.com

Reposted by Mir Lab

Patrick S. Mitchell @psmitchej.bsky.social · Feb 21

In light of policies to defund biomedical research, and with judicial hearings happening today, we hope to highlight the many ways biomedical research improves people's lives, and to convey how damaging the proposed cuts would be... not just for us researchers, but for everyone.

Jakob von Moltke @jmoltke.bsky.social · Feb 21

Patrick Mitchell (@psmitchej.bsky.social), Thornton Thompson and I wrote an OpEd, with support from 650+ biomedical researchers across Washington State (450+ at time of submission).

www.heraldnet.com/opinion/comm...

List: www.moltkelab.com/s/NIH-OpEd-S...

Comment: Pending cuts to medical research would harm all in state | HeraldNet.com

As UW medical scientists, we urge Washingtonians to defend the NIH’s life-saving research funding.

www.heraldnet.com

Mir Lab @mirlab.bsky.social · Feb 12

And all the MS2 interaction analysis was done by an amazing bioengineering graduate student @manyakapoor.bsky.social who just joined Bsky!

Mir Lab @mirlab.bsky.social · Feb 12

Major oversight in my earlier postdoc: This work was led by our wonderful postdoc @mukherja.bsky.social who also built the microscope that enabled these experiments

Mir Lab @mirlab.bsky.social · Feb 12

We can't follow the same cluster but see a shift in cluster kinetics across nuclei. We can't say anything about initiation factors since we are just looking at pol2 and we are testing effects of recruitment vs elongation with the drugs. Will check our language to make sure this is clear. Thanks.

Mir Lab @mirlab.bsky.social · Feb 12

7/n Overall we show that Pol II clusters are functionally labile and suggest that they likely represent collections of molecules engaged at a single gene locus. Please take a read and send us your critical feedback!

Mir Lab @mirlab.bsky.social · Feb 12

6/n Using simultaneous imaging of nascent transcription and Pol II clusters we found that a single cluster remains associated with an active gene during a transcription burst and the intensity of the cluster is highly correlated in real time with the amount of nascent transcription.

Mir Lab @mirlab.bsky.social · Feb 12

5/n Using inhibitors of initiation and elongation we found that cluster formation is dependent on initiation and that transcription elongation leads to a reduction in cluster lifetime.

Mir Lab @mirlab.bsky.social · Feb 12

4/n We found that Pol II clusters undergo a transformation as the zygotic genome is activated. From initially being mostly composed of molecules engaged in transcription initiation to becoming hotspots of elongating molecules.