Timothy (Tim) Silas Strutzenberg is a NOMIS–Salk Fellow at the Salk Institute for Biological Studies in La Jolla, US, where he is conducting research under the mentorship of Dmitry Lyumkis.
Strutzenberg is a biochemist from Des Moines, Iowa (US). He completed his undergraduate studies at the University of Iowa in 2015 and his PhD at the Scripps Research Institute in 2021. His projects sought to understand how the transcription factor protein RORγt is regulated by small molecules and DNA. RORγt plays important roles in the immune system and is a major target for pharmaceutical development to treat chronic autoimmune disorders like multiple sclerosis and plaque psoriasis. During his thesis project in the lab of Patrick R. Griffin, Strutzenberg developed techniques to interrogate protein structure and dynamics using mass spectrophotometry and x-ray crystallography, which he used to define the origin of RORγt activities in the cell and describe how small molecules modulate RORγt to elicit diverse functional outcomes.
Research Focus
In 2021 Strutzenberg joined the Lyumkis lab, which studies fundamental processes involving chromatin regulation and its role in disease. Here, he initiated efforts to employ cryogenic electron microscopy (cryo-EM) and chromatin biochemistry to study nuclear receptors. He developed novel biochemical techniques to determine how RORγt can bind to nucleosomes. Strutzenberg then solved the first structure of RORγt interacting with the nucleosome using cryo-EM and identified allosteric effects that influence RORγt binding and mediate chromatin dynamics. His work suggests a novel activation model for how RORγt engages chromatinized DNA to promote transcription.
As a NOMIS–Salk Fellow, Strutzenberg aims to interrogate how RORγt works cooperatively with other proteins to regulate the expression of its target genes in T cells. To do this, he is extending his training to learn T cell biology in mouse models of disease and novel chromatin profiling techniques. The goal of his work is to gain fundamental insights into how and why RORyt regulation depends on cellular context; build a more holistic understanding of why RORγt activates pro-inflammatory genes in T cells; and understand how this results in autoimmunity. This research will have implications for developing novel therapeutics for diseases and will enable Strutzenberg to expand into other exciting areas of chromatin biology.
Feature image: Tim Strutzenberg portrait. Right: Atoms of a protein are placed in a coulombic potential map solved by cryogenic electron microscopy. (Photos: Salk Institute)