Dissertation / PhD Thesis

PUBDB-2025-04050

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Structural Biology in Action: Investigating EGFR Mutations in Lung Cancer and Engineering Biosynthetic Enzymes

Zhang, L.Extern*

2025

Abstract: This thesis explores the role of structural biology in understanding protein function, with a primary focus on EGFR mutations in NSCLC (Part I) and a secondary focus on enzyme engineering for biotechnological applications (Part II). Part I of this thesis investigates how EGFR kinase domain mutations alter protein stability and inhibitor sensitivity through computational modelling, providing insights into drug resistance mechanisms and treatment outcomes in NSCLC patients. Additionally, it examines the role of Molecular Tumor Boards (MTB) in guiding targeted therapies for patients with rare or complex mutational profiles, not only limited to EGFR, but also includes ALK, BRAF MEK and other genes, highlighting the clinical implications of structural insights. Part II of this thesis shifts to an experimental structural approach, focusing its application on protein engineering and enzymatic function. It explores the structural characterization and engineering of a plant polyketide synthase for the biosynthesis of methylated flavonoids, an area of interest for pharmaceutical applications. Additionally, it investigates the substrate specificity and catalytic mechanisms of two bacterial O-methyltransferases, shedding light on their potential in biocatalysis.Whether in assisting precision cancer therapies or engineering enzymes for biocatalysis, the ability to decode protein structures remains a cornerstone of scientific discovery. The studies in this thesis also underscore the complementary roles of computational and experimental methods in structural biology, demonstrating how theoretical predictions and empirical observations together enhance our understanding of protein function, ultimately advancing both fundamental science and its translational applications.

Note: Dissertation, University of Groningen, 2025

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Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)

Experiment(s):

1. PETRA Beamline P11 (PETRA III)
2. PETRA Beamline P13 (PETRA III)

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