Please join the Department of Chemical and Biological Engineering on Thursday, September 21 at 9:30am in Frances Searle 1421 for student seminars by Derek Wong and Maddie DeWinter in the Jewett Lab.
Derek Wong will present a seminar over Zoom titled "Developing a cell-free workflow for characterizing antimicrobial peptide biosynthesis.”
ABSTRACT: Antimicrobial resistance continues to be one of society’s greatest health threats, causing over 1.2 million deaths per year. With the emergence of multi-drug resistant bacteria, it is imperative that we develop new antimicrobial molecules. Antimicrobial peptides, which are produced by a wide array of microorganisms as part of their immune system to protect against pathogenic microbes, have demonstrated great success as antimicrobial agents. One diverse source of antimicrobial peptides are ribosomally synthesized and post-translationally modified peptides (RiPPs), which are natively produced by a wide array of microorganisms. Composed of an amino acid peptide backbone, RiPPs are produced by the ribosome and subsequently modified with additional tailoring enzymes. A key first step in the biosynthesis of over 50% of RiPPs is the recognition of the peptide backbone by the RiPP recognition element (RRE), an enzyme that guides tailoring enzymes to the proper peptide substrate. During my PhD, I developed a cell-free workflow for expressing, detecting, and characterizing the binding activity of RREs. In this talk, I will discuss two examples utilizing this workflow for understanding and engineering RiPP biosynthesis. First, I will describe how this workflow can be used to interrogate residues important for recognition by an RRE and subsequently be used to engineer new-to-nature peptides recognized by a desired RRE. Then, I will demonstrate how this workflow can be used as a screening tool when coupled with computational prediction tools to enable the discovery of novel RiPPs. Ultimately, this platform for screening and characterizing RREs will accelerate the discovery and engineering of novel RiPP molecules with antimicrobial activity.
Maddie DeWinter will present a seminar titled "Accelerating discovery and improving access to protein and peptide-based therapeutics using cell-free protein synthesis.”
ABSTRACT: Biologic therapeutics are an increasingly popular class of medications that can treat a wide variety of ailments, including infections, cancer, autoimmune diseases, and certain hereditary conditions. Although these medications have been transformative, they take approximately a decade to develop and can be difficult to deliver to resource-limited settings. In my PhD, I have been addressing these issues using cell-free protein synthesis, an in vitro method of synthesizing protein using transcription and translation machinery from cells. One of the most common protein-based medications are antibodies, which rely on binding to target antigens to function. Pre-clinical development and selection of lead antibody candidates, which can take up to 18 months, often relies on inoculating animals with the antigen of interest or collecting the serum of humans who have recovered from disease. Computationally designing de novo protein binders presents an opportunity to circumvent the weeks-long process of an immunologic antibody selection by creating protein binders in silico. However, computational algorithms still need to be improved so that first-pass binder designs have the desired properties. Towards this front, I have successfully initiated an mRNA display in vitro selection platform to test and further improve computational binder design. Additionally, once a biologic has been developed, it is still very difficult to distribute those products to resource-limited settings as they are inherently unstable and must be kept within strict temperature guidelines. To address this, I have designed a platform for decentralization of peptide hormone manufacturing wherein we use lyophilized cell-free protein synthesis reactions to synthesize and purify these medications at the point-of-care. In total, my PhD work has focused on improving time to development and access to protein and peptide-based medications.
Bagels and coffee will be provided at 9:30am, and the seminar will start at 9:40am. Please plan to arrive on time to grab a bagel and mingle!
*Please note that there will be no Zoom option to attend seminars this year.
