Congratulations to Tae-Eun and Kotaro for successfully publishing the Rocklin Lab's first paper!! Congrats as well to Cydney and Claire who played important supporting roles. We learned a lot between our initial submission and our revised version, including that some fraction of the designs are dimers and that our original NMR structure was actually a dimer! Thanks to Tae-Eun's persistence and the hard work of Scott Houliston, we actually solved a second NMR structure and collected a second set of HDX data for a monomeric protein. Check it out either at PNAS or see our revised manuscript on bioRxiv.
Dissecting the stability determinants of a challenging de novo protein fold using massively parallel design and experimentation Kim*, Tsuboyama* et al. PNAS 2022 bioRxiv Open Access Link This paper
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It has been a busy summer! Here are some updates from the lab: In May the whole lab attended the Midwest Folding Conference in South Bend, IN. Gabe gave the closing talk! At the start of the summer we said goodbye to our Rosetta Commons postbac Andres Lira. Andres is off to graduate school in biophysics at the University of Wisconsin-Madison! DGP Ph.D. student Tanu Priya joined the lab in June to work on enzyme design! Welcome Tanu! DGP Ph.D. student (and lab founder) Claire Phoumyvong passed her qualifying exam! We hosted three summer undergraduates this summer: Rosetta intern Sarah Fahlberg, Northwestern Synthetic Biology REU student Cassie Chrisman, and Northwestern Summer Undergraduate Research Grant awardee Yulia Gutierrez! It was our pleasure having all of you here for the summer! Five lab members (Suggie, Jane, Állan, Claire, and Sarah) attended RosettaCon in Leavenworth, WA, the first in-person RosettaCon since before Covid! Jane was selected to give a talk on her high-throughput hydrogen-deuterium exchange work! Wow that was even busier than I remembered. Onward to fall!
Tae-Eun and Kotaro finished the lab's first preprint!! The title is "Dissecting the stability determinants of a challenging de novo protein fold using massively parallel design and experimentation."
Read it here: https://www.biorxiv.org/content/10.1101/2021.12.17.472837v1 And see Tweet threads from me and Kotaro! I really like this paper for a few reasons. First, Tae-Eun started this project during his very first week in the lab- the second week after I arrived at Northwestern. Then Kotaro made significant contributions while he was still in Japan before arriving in Chicago. The paper examines a puzzle from my previous work with protein design- why the alpha-beta-beta-alpha fold (or HEEH as we often call it) and such a lower success rate than the other designs in my 2017 paper. Tae-Eun and Kotaro examined this question in depth and designed thousands of new stable proteins. We also collected some cool hydrogen-deuterium exchange data on an HEEH designed protein. This paper also provides one of the first pieces of evidence that AlphaFold 2 is not a panacea for protein design - many of the unstable designs look just as good as the stable designs according to AlphaFold 2. Cydney and Claire also contributed to this paper, so that makes five Rocklin Lab authors! We are excited to see this published! At the end of June we said farewell to two long-time researchers in the Rocklin Lab. Radhika Dalal finished her time as a Rosetta Commons Post-baccalaureate Scholar and is now preparing to start her Ph.D. research at UCSF's Biophysics program! We are so excited for her! Unfortunately Radhika could only work remotely for her entire time with us, but we will miss her. Good luck at UCSF Radhika!!
Jonathan Chen also graduated from the lab after completing his Master of Science in Biotechnology degree. Congratulations Jonathan! Jonathan is moving on to a position at Kite Pharma and might be considering a Ph.D. in protein design in the future! Jonathan leaves behind tens of thousands of designed proteins that we have not yet experimentally tested, but we expect to have these results soon :). Jonathan will really be missed - in addition to being a great colleague he was also a mentor for many summer and rotation students in the lab. Along with sad goodbyes, we are also excited to welcome many new lab members! We are so thrilled that lab founder Claire Phoumyvong (Research Technician March 2019-Aug 2020) has decided to re-join the lab as a DGP Ph.D. student!! We are also excited to welcome two scholars supported by Rosetta Commons: Will Howe (Rosetta Commons Summer Intern) and Andres Lira (Rosetta Commons post-baccalaureate fellow). Matthew Jin has also joined the lab as a Northwestern Synthetic Biology Summer REU student! Finally, Kyrollos Shenouda joined the lab for his Northwestern Master of Science in Biotechnology research. Welcome Kyrollos! With so many new people we are all being kept busy, but it has certainly made the lab lively! Also: congratulations to Cydney Martell for passing her qualifying exam! Hi, I want to get in the habit of sharing lab news more, so let me do a big dump of lab news from the lab's second year. Certainly the past year was a painful year for the world and wreaked havoc on the lives of our lab members to varying degrees. But I think we can be proud of the ways we tried to stay connected over the past year and the progress people were able to make despite the pandemic. So, here's a summary of some of the big achievements of the lab's second year-
Lots of new people joined the lab! Cydney Martell joined the lab as our 2nd PhD student from the DGP program. Will Corcoran also joined the lab as a joint student with Josh Leonard's lab (Will was previously just advised by Josh). Jane Thibeault joined the lab as our third postdoctoral fellow, soon followed by Állan Ferrari who just started as our fourth fellow. Both Jane and Állan have backgrounds in proteomics and computation. Radhika Dalal joined the lab as a Rosetta Commons Postbaccalaureate Fellow! We won some awards! The lab was awarded our first external grant - a prestigious NIH New Innovator award. This award will support our work to develop a high-throughput hydrogen-deuterium exchange approach to study protein energy landscapes. Kotaro Tsuboyama started his fellowship as a Long-Term Fellow of the Human Frontiers Science Program! Állan Ferrari was awarded a BEPE Fellowship! Cydney Martell was awarded a competitive spot in Northwestern's Center for Life Processes Training Program! Will Corcoran was awarded a competitive spot in Northwestern's Biotechnology Training Program! We hosted summer students! Jordan Gewing-Mullins and Nahtalee Lomeli worked with us remotely over Summer 2020. Some of us moved on... Our first lab member Claire Phoumyvong moved on to join Northwestern's DGP Ph.D. program. She is now back rotating in our lab though :) One of my goals this year is to update the website more frequently, so hopefully there will be more news soon! Postdoctoral positions in high-throughput protein biophysics, machine learning, and design The Rocklin Lab (www.rocklinlab.org) is seeking multiple postdoctoral fellows for experimental and computational projects. We are located in a brand new building on Northwestern’s medical campus in downtown Chicago, in a space dedicated to Northwestern’s Center for Synthetic Biology. Start dates are flexible. About us Our group focuses on applying high-throughput technologies to protein biophysics and protein design. We construct libraries of thousands of proteins (de novo designed or naturally occurring), assay their properties using multiplexed methods, and analyze these datasets to understand how protein phenotypes arise from protein sequence and structure. These insights enable us to design new proteins with unique properties. For examples of this approach, see Rocklin et al. 2017 and Chevalier et al. 2017. One of our exciting new experimental tools is an approach to measure conformational fluctuations for thousands of proteins in parallel using hydrogen exchange mass spectrometry (see poster). We are using this unprecedented large data to examine:
Position description We are looking for interested researchers from any scientific specialization, including biology, chemistry, physics, and computer science. We are especially interested in expertise in hydrogen exchange mass spectrometry, protein biophysics, and machine learning, but please apply if you are interested and bring a different specialization. Computational research will be entirely remote during the Covid-19 pandemic. Why join the Rocklin Lab? We are building a multidisciplinary and collaborative group in a fantastic environment. Our researchers are integrated into several larger communities that expand their scientific reach, including Northwestern’s synthetic biology community (https://syntheticbiology.northwestern.edu), Northwestern’s proteomics community (http://proteomics.northwestern.edu), and the international Rosetta protein modeling and design community (https://www.rosettacommons.org). Please visit rocklinlab.org or email grocklin@gmail.com to learn more. To apply, please email me your CV and a cover letter describing your interests. ![]()
Last week we officially moved into our space in the brand new Simpson Querrey building! We're very excited to share the wet lab space along with our Center for Synthetic Biology buddies in the Prindle Lab.
Thank you so much to Claire, Wes, and rotation students Katiannah and Aishwarya for all your work to make the move go smoothly! It's beautiful here! Here's a talk I gave to the incoming DGP students about why they should rotate in our lab. We have at least six rotating students in 2019-2020! ![]()
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Gabriel RocklinAssistant Professor Archives
October 2022
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