Michael Kosicki

@ATinyGreenCell Can you get it to go inside the virus or inside the cell just infected with a virus? Small molecule inhibitors mostly work because they can.

Can we make a nanobinder for the integrase?

Probe-based scRNA-seq + makes modern perturbation genomics cheap and flexible - highlighting ProPer-seq m/s I was lucky to contribute to @LukeGilbertSF's lab biorxiv.org/content/10.648…

@JulioSongC What's your personalization prompt? Mine helps me a lot, clear difference with a clean session I sometimes open on my phone.

Lately I've grown increasingly annoyed by ChatGPT's hallucination, verbosity & eagerness to censor/preach, so I've switched to Gemini&Grok for a change. So far I'm loving them both!🫡 A truly refreshing experience! As a user, I think ChatGPT has forgotten what it's meant to be.🙄

@TanentzapfLab I find it's an excellent filter both ways - if I do not find anyone I could imagine working with, why apply? Also, if the committee is upset enough about including someone to deal you out - bullet dodged.

Advice from having served on faculty search committees: ALWAYS list in cover letter faculty at place you are applying to whose research aligns with yours & that you could work with. At the very least it shows you're interested enough to put minimal effort to visit their webpage.

#CELLFIE for CAR T screening, out in @Nature today—a new mRNA-based platform for screening primary cells. CAR + gRNA library are delivered by lentivirus, CRISPR modifiers as electroporated mRNA. That’s more flexible and effective than existing T cell screening methods. (1/7)

The ability to design antibodies against any protein of interest has major implications for medicine, biotech, and basic science. Today, we introduce Germinal, a pipeline for epitope-targeted de novo antibody design achieving  4–22% success rates with efficient experimental validation.

New faculty position opening @Stanford_ChEMH. Especially interested in candidates with deep expertise and vision for the future of AI/ML/computational models of biomolecules. Please RT

🚨Exciting opportunity! (In addition to post-doc openings), we’re hiring an In Vivo Research Scientist w/ @genophoria (Hani Goodarzi's Lab) @arcinstitute (Palo Alto): shorturl.at/zqW9l Experience with advanced in vivo work preferred (survival surgeries, etc.).

Online now: Efficient stem cell-derived mouse embryo models for environmental studies dlvr.it/TMl3LF

I'm thrilled to share that I'll be starting my lab (greenwald-lab.org) at the Lunenfeld-Tanenbaum Research Institute @SinaiHealth and joining @MoGen_Grad at the University of Toronto as an assistant professor this fall. 1/

@jengreitz & I are looking to hire a computational biologist/biostatistician with project management expertise to collaborate with our teams to map the regulatory code of the human genome and discover genetic mechanisms of disease. Details below careersearch.stanford.edu/jobs/computati… Plz RT

✨Not a rainbow trout… a rainbow zebrafish 🌈 🐟 The expression of 10 different genes simultaneously including Hox genes along the body axis, somites, brain regions, skeletal muscle, and heart 🔬Video by Alice Sherrard, Gabby Jerz & Nipam Patel 🧪 #FluorescenceFriday

The Sudmant lab at UC Berkeley is seeking a postdoc to work on a fully funded NIH project to understand differences in DNA repair and somatic mutation across the primate tree of life. Please spread widely to those who may be interested aprecruit.berkeley.edu/JPF05052

@SashaGusevPosts @markmccarthyoxf While it's a problem for modeling complex diseases, I wouldn't demonize it - physicians (and patients) often need to make a fairly binary decisions. It's complicated and of unknown utility to e.g. take statins proportional to your PRS. For now.

@markmccarthyoxf Yes, a much more common problem than I would have ever expected. And something that has to get solved as we develop more and more integrative/multifactorial predictive models.

I wrote about how genetic risk works in the context of embryo selection and how people often think about it all wrong. A short 🧵:

I am thrilled to share that I will be starting my lab in the Center for Pediatric Neurological Disease Research (CPNDR) at St. Jude Children’s Research Hospital as a faculty member @StJude @StJudeResearch. Deeply grateful for the incredible mentorship, support and camaraderie in the @Sergiu_P_Pasca lab. In this next chapter at St. Jude, the Chen lab is hiring postdoctoral research associates and welcomes visiting students and scholars to join us!!! Our lab aims to accelerate therapeutic development for brain disorders, leveraging human (stem cell)-derived models and gene targeting tools. Research themes: - How do genetic variants contribute to pediatric neurological disease at the molecular, cellular, circuit and organismal levels? - How can we push the boundaries of human-derived models to tackle disease (e.g., benchmarking 3D culture and high throughput drug discovery)? Interested? Reach out for collaborations or apply for postdoc positions 👇: talent.stjude.org/careers/jobs/J… Postdoc Benefits (including a 7% 403b match): stjude.org/education-trai… #postdoc #organoids #Neuroscience

This paper is really elegant and beautiful. Researchers took a vesicle, filled it with a single type of enzyme and some protein pores, and showed that this "minimal cell," made from just three components (!!), could "actively propel itself toward an enzyme substrate gradient." Here are some more details on what they did and why this is so cool. First, they encapsuled one enzyme (either urease or glucose oxidase) into the vesicle. They also included some pore proteins (α-hemolysin) to allow molecules to freely diffuse into, and out of, the vesicles. Next, these loaded vesicles were put in a microfluidic chamber with a substrate gradient (either glucose or urea) and watched under a microscope. Vesicles without any pores drifted around aimlessly. But, oddly enough, the vesicles carrying a single enzyme and some pores were able to actively move up the substrate gradient. The vesicles loaded with urease, for example, moved 0.3 µm/s up the gradient. (They did not move whatsoever in the y-direction.) This is really surprising to me because these vesicles have no flagellum or energy source. Indeed, they don't have any obvious mechanism to move whatsoever! All they have is this one enzyme and some pores poked in the vesicle's membrane. The researchers, appropriately, tried to explain how these vesicles move in the paper. Here's what they think is going on. When you drop a vesicle into a chemical gradient, there is a different concentration of molecules on each side. One side of the vesicle is "exposed" to a higher concentration of, say, urea than the other side. These molecules bump into the vesicle and tug on it, but generally the effects are random and small. But now, if you add an enzyme and a pore to that vesicle, it isn't passive anymore. Substrates are diffusing into the vesicle, and then the enzyme inside is transforming them and spitting out new products. These new "products" build up inside the vesicle and need to escape through the pores. This gradually sets up a tiny imbalance in chemical concentrations around the vesicle, which is enough for the vesicle to basically recoil from its own "exhaust pipe." Note that this effect is REALLY different for different enzymes. Urease triggered the fastest movements, whereas other enzymes led to much smaller effects. It all depends on how quickly the enzyme makes products, what those products are, how many pores are in the vesicle, and so on. There are a lot of variables. But still, the researchers ran LOTS of control experiments for this paper just to be sure this wasn't a fluke. They watched and recorded "empty vesicles, empty vesicles with pores..." and other controls, too. None of them had any "appreciable difference in drift." The movements were "only observed when vesicles incorporate both an encapsulated enzyme and functional pores." I really like this paper (and all its math equations), because it shows just how complicated it can be to understand even a super simple biochemical system; in this case, a system made of little more than a vesicle, an enzyme, and a pore.

Our Issue 07 launch party in San Francisco was a smashing success. 🏏 Thanks to everyone who came and played Biology Trivia. Winning teams got copies of our DNA books, hats, and posters. It was a really fun time! See you in the fall, in Boston, for the next one. :)

Range extender mediates long-distance enhancer activity nature.com/articles/s4158…

nature.com/articles/s4158… Wow! 1,700 transgenic mice for the most comprehensive enhancer characterization ever. Leo and Axel never cease to amaze!

Postdoc position opening in my group! Research projects: pangenomes for diverse organisms, genome evolution, biocomputing, language models. Please reach out if interested!