MSc thesis Position in Triple-Negative Breast Cancer Organoids

MSc thesis Position in Triple-Negative Breast Cancer Organoids

Patient-specific drug response and scRNA transcriptomics in TNBC organoids

The Kessler Lab at the Department of Gynecology and Obstetrics (LMU University Hospital) is looking for a highly motivated and skilled master's student to join our project analysis of patient-specific drug response in triple-negative breast cancer (TNBC) organoid model.

TNBC is the most difficult-to-treat type of breast cancer, due to the absence of molecular markers that can be effectively targeted by specific therapeutic agents. Despite the addition of immunotherapy to the course of treatment, systemic chemotherapy remains an important component of the TNBC treatment guidelines. Despite neoadjuvant treatment some patients fail to show pathologic complete response (pCR), leading to less favorable long-term prognosis. We have generated long-term stable organoid lines from selected TNBC patients as a robust model to study in vitro dynamics of the response to different therapeutic agents and analyze cellular phenotypes of surviving clones. Key methods in performing organoid work, such are drug testing assays, and phenotypic analysis of organoids (IF staining, qPCR, WBs) are established and routinely performed in the lab. The group has long-standing experience and expertise in patient-derived organoid models in gynecological oncology as contributed seminal works in the field (Trillsch et al 2023, Hoffmann et al., EMBO journal 2020, Kessler et al., Nature Communications 2015 and 2019).

Project goals

Perform drug test assays on TNBC organoid lines (PARP inhibitors, antibody-drug conjugates), drug response curves, and conditions for survival and resistance mechanisms. To characterize the cellular architecture of the TNBC organoids, and analyze the expression profile of the drug response on the single-cell level, single-cell sequencing will be performed (10x platform). A systematic comparison of the in vitro model to parental tissue will be performed by spatial transcriptomics (Visium). As a member of our interdisciplinary research team, you will get the opportunity to obtain training and gain experience in comprehensive cell culture and molecular biology techniques required for work with organoids (cultivation, clonal expansion, multiwell assays, imaging). You will also help in data analysis, obtain a theoretical background in adult stem cell biology and molecular oncology, and deepen your understanding of cellular mechanisms that drive response to therapy and occurrence of resistance.

Start

As soon as possible, summer semester (2024).

Interested students of Biology, Biochemistry, or related subjects should send an application including motivation letter, CV, and transcript of records by mail to Dr. Mirjana Kessler ([email protected])