CSB Student Profile: Clay Tydings

Posted by daviskd2 on Friday, February 7, 2025 in News.

Teamwork makes the dream work! Clay Tydings, of the Walker and Meiler Labs, thinks collaboration is key to not only furthering his scientific endeavors but also for achieving a personal goal. Meet Clay …

What is the focus of your research and what tools/techniques do you use?

I work on developing methods for modeling peptides with non-canonical amino acids, such as sidechain conjugations. As computational modeling of molecular systems has improved, a new paradigm has emerged: in silico first. For molecules such as peptides, we can now use computation to generate hit compounds as determined by experimental validation.

As a focus of my PhD work, I develop protocols in Rosetta that can assemble peptides with complex ring topologies, including adjacent and overlapping rings and peptides that contain rings within other rings. Specifically, I’ve been working to implement parameters to model the lanthionine rings found in lanthipeptides, a class of ribosomally synthesized and post-translationally modified peptide (RiPP). Lanthipeptides are natural products that gained interest due to their antibacterial properties.

Additionally, I use Rosetta and molecular dynamics simulations in Amber to develop therapeutic peptides. My current focus it to develop peptide agonists for the Y4 receptor and peptides which target the epidermal growth factor receptor (EGFR). Activation of the Y4 receptor promotes satiety, so peptides could potentially serve as anti-obesity therapeutics and dysregulation/overexpression of EGFR is implicated in numerous cancers which would benefit from therapeutic intervention.

What was your path to this position?

My research journey began studying chemistry as an undergraduate at Carleton College. During two subsequent summers, I participated in the National Science Foundation’s Research Experiences for Undergraduates. My first summer was spent at Kettering University in Flint, Michigan, where I worked to advance a cell segmentation model for stained plant tissue images. The following summer, I worked at UCLA developing a machine learning model that could predict apoptotic commitment of cells to inform how they use information to make an apoptotic commitment.

Following my undergraduate studies, I enrolled in the chemistry PhD program at Vanderbilt and joined the Walker and Meiler labs. These labs have enabled me to develop and apply methods for peptide modeling and design as well as foster collaborations with the scientific community at large. I’ve been given the opportunity to work with Dr. Annette Beck-Sickinger at Leipzig University to study peptide–GPCR interactions and with Dr. Bhuminder (Bhumi) Singh at VUMC to study the effects of EGFR resistance mutations in colorectal cancer and to test potential EGFR targeted therapeutic peptides. I recently published a review article titled Analysis of EGFR binding hotspots for design of new EGFR inhibitory biologics with Bhumi and other EGFR Meiler lab collaborators.

What is your favorite part of performing research within a lab?

I enjoy discussing my ideas with awesome people and talking about their own interesting concepts. The free-flowing and thought-provoking conversations enable me to learn about the scientific approaches of my lab mates and apply them to improve the quality of my own science. Finally, every day I investigate the structures of complex biomolecules and get to look at beautiful pictures of proteins and peptides that enable me to gain deeper insight into their behavior.

What are some fun activities you like to do outside the lab?

Outside the lab, I’m involved in St. Augustine’s episcopal church, the church on Vanderbilt’s campus. I’m also active in the Nashville running community as a member of the Nashville track club. Last October, I ran a 2:34 marathon in Columbus, Ohio. With that qualifying time, I plan to run the Boston marathon in 2026.