Page 31 - Hormel Report 2021

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Publications:
• Iva Chitrakar, Syed Fardin Ahmed, Andrew T. Torelli, and Jarrod B. French (2021) Structure of the E. coli Agmatinase, SPEB. PLOS ONE 10.137/journal.pone.0248991
• Yue Yin, David Frank, Weijie Zhou, Neena Kaur, Jarrod B. French*, and Nick Carpino* (2020) A 2H-phosphoesterase activity of suppressor
of T-cell receptor signaling-1 contributes to the suppression of cell signaling. J. Biol. Chem. 295(25): 8514-8523.
• Iva Chitrakar, James N. Iuliano, YongHe Le, Jinnette Tolentino Collado, Jinelle Wint, Stephen G. Walker, Peter J. Tonge, and Jarrod B. French (2020) Structural basis for the regulation of biofilm formation and iron uptake in A. baumannii by the blue-light using photorecoptor, BlsA. ACS Infect. Dis. 6(10): 2592-2603.
Figure 1: Mechanisms of assembly of higher order structures: The protein Uridine Monophosphate Synthase is involved in making the building blocks for DNA and is an important target for the development of new cancer treatments. We have identified new ways that this protein assembles into larger, polymeric structures in order to control its activity level.
Targeting the Suppressor of TCR Signaling (STS) proteins as a means to enhance the immune response to treat infections by deadly pathogens – The Suppressor of T-cell Receptor Signaling (STS) proteins are negative regulators of anti-fungal and anti-bacterial responses. With our collaborator Nick Carpino at Stony Brook Uni- versity, we have found that knock-out of this protein in in vivo leads to a profound resistance to infection. We are working to identify small molecule inhibitors for STS-1 as candidates for a potential immunomodulatory drug (Fig. 2). Such thera- pies could be broadly applicable against a wide variety of microbial pathogens.
Structural Dynamics and mechanisms of BLUF and LOV photoreceptor signaling – together with our colleague Pete Tonge (Stony Brook U.) we are working to understand how signal transduction occurs in specific photoreceptors, called BLUF and LOV photoreceptors. These proteins are becoming increasingly import- ant for optogenetics – the use of light to control the function of biomolecules. This technology can be used to selectively target treatments or control the timing of drug release.
Identification and characterization of novel nucleobase transport proteins –
we are developing chemical probes and assays to identify new classes of proteins that control how purine and pyrimidine nucleobases enter and exit cells. Many types cancer and infectious diseases are treated with drugs that are structural analogs of nucleobases. The discovery and characterization of these transport proteins has the potential to accelerate the development of more effective anti- cancer and antiviral therapies with fewer side effects.
Figure 2: Targeting Sts proteins to stimulate immune responses