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Student Class

2024

Student Affiliation

Senior Honors Thesis

First Advisor

Henry Higgs

First Advisor Department

Geisel School of Medicine

Second Advisor

Sukrut Kamerkar

Second Advisor Department

Geisel School of Medicine

Description

In this poster, I summarize my work exploring the dynamics and cellular function of the novel protein LactB. LactB is a bacterial penicillin-binding protein homolog and mitochondrial serine protease whose function is not fully understood. LactB localizes to the intermembrane space (IMS) of the mitochondria and forms filaments. However, it is unclear where LactB functions within the IMS, or whether it interacts with the mitochondrial membranes. Furthermore, LactB acts as a tumor suppressor in colorectal cancer, hepatocellular carcinoma, glioma, melanoma, gastric cancer, lung cancer, and ovarian cancer. The mechanism for LactB’s tumor suppressor function is debated, though a number of pathways have been proposed.

My research focuses on two subjects: 1) the dynamics of LactB within the IMS via fluorescence recovery after photobleaching and 2) the effects of LactB knockout and knockdown on cellular function by examining lipid droplets and apoptosis. Although I found the LactB-GFP construct I used to have an immobile fraction in the mitochondria, my work with FRAP was discontinued after the publication of LactB’s CryoEM structure revealed structural complications with this construct. Instead, I focused on siRNA knockdown and CRISPR-Cas9 knockout exploring the impact on lipid droplets, spherical organelles important in lipid metabolism and tumorigenesis. I found significant changes in lipid droplet size and number in two melanoma cell lines. I also explored the effects of decreased LactB expression on apoptosis, finding a decrease in apoptosis in one cell lines. My studies raise the important question of the mechanism by which LactB contributes to apoptosis.

Publication Date

Spring 5-22-2024

Keywords

biochemistry, biology, cancer, mitochondria

Disciplines

Biochemistry | Biochemistry, Biophysics, and Structural Biology | Biology | Cancer Biology | Cell Biology

Comments

Christopher Reed Science Competition: 3rd Place

In Pursuit of Understanding the Physiological Mechanism of the Tumor Suppressor LactB

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