BATS

Date/Time:

May 24, 2024 - 12:00 PM

Location:

Hosts:

Bevin Engelward

Speaker:

Title:

Engineering a Knottin Inhibitor of Tumor Necrosis Factor

Abstract:

Knottins are small, disulfide-rich peptides that exhibit exceptional stability to extremes of pH, heat, and protease concentration. Their solvent-exposed loops are amenable to mutation, raising the possibility of engineering them into orally available mini binders. Such binders could be used as protein-protein interaction inhibitors for gastrointestinal indications – similar to how the antibody drug Humira can block autoimmune activity by blocking tumor necrosis factor (TNF) from binding its receptor on immune cells. We aimed to create a yeast surface display platform to accelerate knottin binder development to any target protein, focusing first on TNF. We have isolated a knottin TNF-binder, affinity-matured it, and characterized its protease-resistance, activity, and unique conformational characteristics.

Speaker:

Title:

Uncovering Translational Mechanisms of Control Over Virulence in Enterohemorrhagic E. coli O157:H7 (EHEC)

Abstract:

EHEC is a foodborne pathogen that precisely coordinates expression of its resource-intensive Type III Secretion System (T3SS) to successfully form lesions within the host. Complex transcriptional networks govern T3SS gene expression, but post-transcriptional regulation is comparatively understudied. Here, we demonstrate that T3SS genes exhibit codon biases relative to genome averages. Further, EHEC reprograms its tRNA pool in response to the hormone norepinephrine to match those codon biases. This work provides a case for codon-biased translational regulation as an additional layer of control over EHEC’s virulence program.