bugajlab.bsky.social
Asst. Professor @ Penn Bioengineering. Cell Signaling, optogenetics, synthetic biology, cancer signaling, regenerative medicine, bio-tinkering. www.bugajlab.com
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including: Ken Lau, Thea Tlsty, Gordon Mills, @tme-caf-ecm.bsky.social, Arthur Lander, @mokhalil.bsky.social, @lucaspelkmans.bsky.social, @josh-leonard.bsky.social,
@arjunraj.bsky.social, Matt Thomson, many more
pleasure to co-organize w/ @zevgartner.bsky.social, Laura Heiser, @ajitjohnson.com
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Congratulations Ophir! Quite a past couple weeks for your group!
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congrats to you and your group George!
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thanks Priya! Sitting next to you trading puns for 4 years was formative:)
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Hah! What a great pic. Missed opportunity by ACS.
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Yes!! Congrats John!!
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We like Aviatar because it does with 1 protein what used to require 2, in a modular manner that is straightforward to engineer.
Also, check out Dennis's recent preprint on BcLOV4, a naturally-evolved membrane-binding 'Aviatar' that inspired us to expand the concept to other compartments
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We also developed a "universal" Aviatar that can localize to any GFP-tagged compartment using a weak nanobody, and we used it to localize to stress granules through endogenously-tagged G3BP1
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Aviatar regulated actin polymerization at the membrane and revealed compartment-specific differences of RTK fragments commonly mislocalized in cancer
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Aviatar can target any desired compartment for which a weak binder can be found. We show common targets: plasma membrane, endosomes, Golgi, ER, and microtubules.
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In Aviatar (Avidity assisted targeting), a single light-sensitive protein translocates from the cytoplasm to an unmodified subcellular compartment. Light induces clustering, clustering turns a weak binder to a high-avidity assembly, and Aviatar flies to its target location.
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Phenomenal conceptual and experimental work by Dennis and a fantastic collaboration with @nmrkaygee.bsky.social and @malvinf.bsky.social at ASRC @CUNY, who are uncovering the structural underpinnings of BcLOV4 light- and temperature-dependent dynamics
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and if you have a good idea to improve, Arjun will probably code it in by EOD😂
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Thank you Sunny!
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and the second
www.sciencedirect.com/science/arti...
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Hmm -- issues with the GIFs above: here is the first!
www.sciencedirect.com/science/arti...
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Many additional details and surprises in the paper. Let us know if you are interested in the thermoPlate. Our goal was for others to build and use in their own labs. Big thanks to NSF, NIH, the US taxpayer, and Penn CPE4H for funding. And @cp-cellsystems.bsky.social for the excellent pub process💯.
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We used the thermoPlate to explore stress adaptation to heat shock.We found beautiful stress granule dynamics and memory formation, with differences at each degree of heating. What started as a quick peek at stress granules is now an exciting new avenue of inquiry for the lab.
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Annoyingly, thermodynamics says heat will not stay confined to individual wells, constraining the complexity of our experiments. But we can predict heat spread dynamics over time with our online app, letting us quickly know if our desired experiment is possible.
bugajlab.shinyapps.io/ThermoPlate_...
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The thermoPlate addresses the lack of methods for fast/accurate/precise/robust control of temperature for mammalian cells, in high throughput, under a microscope. Like the optoPlate but for temperature, including 96x PID controllers for precision.
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beautiful results Scott, congrats to you, Rohith, and the lab!
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Thanks Chengwei, will respond shortly!
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actually, they can be! Though more likely this technology could someday be used to control cells in a tumor in response to gentle heating or cooling from an external device -- perhaps even something as simple as an ice pack or heat pad
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Big congratulations to the phenomenal scientists that made this happen: Will Benman and Dennis Huang
@dennishuang.bsky.social, along with assists from many others in lab. Perpetually grateful to work with with such exceptional people. 🙏
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Many exciting possibilities for Melt and thermal control. Reach out if you'd like to try this in your favorite system!
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A major promise of thermal control is the ability for precise, non-invasive communication with cells in vivo. Here, Melt allowed temperature-controlled killing of cancer cells in a mouse, in response to local cooling of the mouse's skin (think ice pack).
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Melt is highly modular and can endow thermal control over signaling, proteolysis, cell shape, and cell death, among other behaviors, through simple end-to-end fusions. Below, Melt-based induction of cell death in cancer cell lines after cooling by ~10C.