Page 29 - Hormel Institute Annual Report 2021-22

Structural Dynamics and mechanisms of BLUF and LOV photoreceptor signaling – Together with our colleague Peter Tonge (Stony Brook University) we are working to understand how signal transduction occurs in a specific class of photoreceptors, called BLUF and LOV photoreceptors. These proteins are becoming increasingly important for the development of optogenetic devices and therapies – optogenetics uses light to control the function of biomolecules. This technology can be used to selectively target treatments to specific sites or specifically control the timing of drug release.
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Recent Publications:
• De Vitto, H., Arachchige, D. B., Richardson, B. C., & French, J. B. (2021). The Intersection of Purine and Mitochondrial Metabolism in Cancer. Cells, 10(10), 2603.
• Chitrakar, I., Iuliano, J. N., He, Y., Woroniecka, H. A., Tolentino Collado, J., Wint, J. M., Walker, S. G., Tonge, P. J., & French, J. B. (2020). Structural Basis for the Regulation of Biofilm Formation and Iron Uptake in A. baumannii by the Blue-Light-Using Photoreceptor, BlsA. ACS Infect Dis, 6(10), 2592-2603.
• Chitrakar, I., Ahmed, S. F., Torelli, A. T., & French, J. B. (2021). Structure of the E. coli agmatinase, SPEB. PLoS One, 16(4), e0248991.
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 struc- tures 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 Univer- sity, we have found that knock-out of this protein in mice leads to a profound resistance to infection. We are currently in the process of developing small molecule inhibitors for STS-1 as lead candidates for a potential immunomodulatory drug (Fig. 2). Such therapies could be broadly applicable against a wide variety of bacterial and fungal pathogens.
Targeting Sts proteins to stimulate immune responses: The Sts proteins are negative
regulators of immune function. Inhibiting these proteins stimulates the immune system and helps the host eliminate dangerous pathogens.