Chemistry and Materials Science Seminar: Thesis Proposals

Chemistry and Materials Science Seminar: 2 Thesis Proposals

PROPOSAL 1
Total Synthesis of D112

George Verhagen
Chemistry MS Candidate
School of Chemistry and Materials Science, RIT

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This seminar may be attended in person in 2305 Gosnell Hall or online via Zoom.

Mr. Verhagen will discuss his thesis proposal, developing a new synthetic route for D112 and produce purified samples for testing on cancer cells. This presentation will discuss the biological activity of D112 and the proposed synthetic route to produce it.

Abstract
Cancer is a serious disease that was the second leading cause of death in the United States in 2019. Cancer is commonly caused by a breakdown of the apoptotic pathway in cells. Arrest of the apoptotic pathways by heat shock proteins is implicated in 24 different types of cancer. The small molecule D112 has shown promise as a prospective cancer treatment by inhibiting heat shock proteins and repairing this pathway, leading to the death of the cancerous cell. However, since its initial discovery by Kodak in the 1970s, information on the synthetic route to produce D112 as well as structural data was unable to be located by Kodak scientists. Our group seeks to develop a new synthetic route for this compound and produce purified samples for testing on cancer cells by Dr. Gary Skuse and coworkers in GSOLS. It is our hope that we can both rediscover a synthetic route to D112, and that this compound continues to show high selectivity and toxicity for cancer cells in testing. This presentation will discuss the biological activity of D112 and the proposed synthetic route to produce it.

Speaker Bio:
George Verhagen graduated with a Bachelor’s degree in biochemistry from RIT in spring of 2021, and entered the Master’s program for chemistry in the fall of 2021. George has done research in the Cody lab since October of 2019, first starting with the preparation of anilines to be used in the synthesis of a photovoltaic dye for organic solar cells. He first became involved with the D112 project in collaboration with the Skuse and Reed labs during the summer of 2021. Currently George is applying his passion for organic synthesis to try to advance the D112 project and produce high purity material with a verified structure for further testing on cancer cell cultures.
 

PROPOSAL 2
Biophysical studies of protein from pathogenic bacteria

Kali Cook
Chemistry MS Candidate
School of Chemistry and Materials Science, RIT

Register Here for Zoom Link
This seminar may be attended in person in 2305 Gosnell Hall or online via Zoom.

Ms. Cook will discuss her thesis proposal, using X-ray crystallography to to determine the structure of two key proteins from pathogenic bacteria with the aim to inform future development of treatments and vaccines against infectious disease

Abstract:
X-ray crystallography techniques can be applied to solve the structures of target proteins. The structural knowledge gained provides insights into protein function and interactions that can reveal new therapeutic pathways. This talk presents the proposed use of X-ray crystallography to determine the structure of two key proteins from pathogenic bacteria with the aim to inform future development of treatments and vaccines against infectious disease. The first protein, VapC, is encoded on a virulence plasmid found in pathogenic enteric bacteria like Shigella flexneri and E. coli O145:H28 strain RM12581, organisms that can contaminate food and have been associated with outbreaks. VapC proteins can cleave tRNA and other RNA molecules with sequence and structure specifically, and this can halt cell growth. We plan to determine the first X-ray crystal structure of a VapC–tRNA complex and to compare VapC RNA binding between two similar, yet different enteric bacterial species for the purpose of providing a foot-hold for future efforts to ultimately control pathogenic bacterial growth by targeting these interactions. Additionally, we are interested in proteins from Non-typeable Haemophilus influenzae (NTHi). NTHi is a leading cause of acute otitis media in children and can cause chronic obstructive pulmonary disease (COPD) in adults. One promising vaccine candidate for NTHi is Protein D, a highly conserved and stable protein in the outer membrane of both typeable and non-typeable strains of Haemophilus influenzae. On its own, Protein D induces an immune response in mice. However, when Protein D is administered with OMP26, the Protein D antibody response is significantly suppressed, which suggests the two proteins are interacting in vivo. Thus, we plan to determine the structure of OMP26 in order to reveal information about protein function and protein—protein interactions which will assist the development of a vaccine against NTHi.

Speaker Bio:
Kali Cook received her bachelor’s degree in biomedical engineering here at the Rochester Institute of Technology (RIT) in May 2021. During her five-year undergraduate program, she completed three cooperative education (co-op) positions. The first was at a small start-up, Health Care Originals in Rochester, NY. There, she assisted the development of a wearable asthma monitoring device by automating data organization procedures using Visual Basic, and later, JavaScript. She applied this programming experience to her second co-op at Fresenius Medical Care North America (FMCNA) in Waltham, MA. As part of a FMCNA operations team, she wrote a program to standardize data received from the company’s dialysis clinics across the U.S. Her last position was in the Preclinical Manufacturing and Process Development Group at Regeneron Pharmaceuticals in Tarrytown, NY. During her time there, she was exposed to the development process behind biopharmaceuticals. This experience sparked her interest in biochemistry, leading her back to RIT to pursue a master’s degree in chemistry. She is currently working as part of Dr. Michael Gleghorn’s research group, focused on studying the structures and interactions of proteins, nucleic acids, and complexes thereof.

Intended Audience:
Undergraduates, graduates, experts. Those with interest in the topic.

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