Taylor Mighell

We think this demonstrates massive potential for pharmacological chaperones for treating a large number of individuals with a broad range of genetic diseases. Check out the pre-print here: biorxiv.org/content/10.110…

There are still important outstanding questions: for example, what fraction of expression-rescued variants are functional? (we are working on this now)

A major challenge in treating rare genetic diseases is the huge number of causal variants in different individuals. This led to assumptions that any given treatment would be suitable only for a small fraction of patients

Very happy to share what I've been working on in Barcelona with @BenLehner ! We made many (>400k) mutations in a disordered peptide and the globular domain it interacts with to gain a comprehensive map of how specificity is encoded in a partially fuzzy protein interaction (1/n)

We presented the first global map of inhibitory allosteric sites for any protein here KRAS and the first comprehensive comparative map of the effects of mutations on the free energies of binding of a protein to multiple partners. nature.com/articles/s4158…

Excited to finally share some of my PhD work on quantifying the effects of indel mutations on protein stability and function using deep mutational scanning. From sunny @CRGenomica together with @ToniBeltran13 and guidance from @BenLehner biorxiv.org/content/10.110…

New preprint from the lab: Deep indel mutagenesis reveals the impact of insertions and deletions on protein stability and function. First paper from Magda with @ToniBeltran13 biorxiv.org/content/10.110…

Time to share my PhD work where we quantified the translational readthrough of thousands of pathogenic stop codons and trained predictive models to predict drug-induced readthrough of any stop codon. With the priceless guidance from @FranSupek +@BenLehner! biorxiv.org/content/10.110…

Very happy to have the first version of the manuscript from my PhD work in @BigSpinLab out!We identify a novel function of the classical NF-κB inhibitor IκBα in regulating pluripotency heterogeneity in mESCs @HMar_research @CarrerasIJC @biorxiv_cellbio #pluripotency #development

if you're interested in mutating long genes or many genes in parallel, give SUNi a try! Code to generate primers here: github.com/lehner-lab/SUN… And feel free to reach out to me with any questions.

More recently I've used SUNi to generate saturation mutagenesis of 5 full-length (~400 amino acids) human genes in parallel (see my poster at Mutational Scanning Symposium if you're interested).

Happy to share published version of SUNi mutagenesis!!: journals.plos.org/plosone/articl… See original tweetorial here to see how we improved nicking primer design for much higher quality libraries: twitter.com/taylor_mighell…

a jupyter notebook to design SUNi primers is here: github.com/lehner-lab/SUN… and stay tuned, we have big plans to use SUNi mutagenesis for human gene-family-scale MAVEs.

The 5' GC clamp finding, combined with a few other tweaks leads to SUNi libraries on average 2x more efficient than standard nicking and importantly, approaching cassette mutagenesis (a method with high quality but low scalability).

Happy to share ☀️SUNi mutagenesis☀️, my first preprint from sunny Barcelona with @IgnasiToledano and @BenLehner. In short, we improve nicking mutagenesis to generate 2x more efficient libraries by improving uniformity and cutting down on wildtype carryover.