PhD Project 8
Identification of molecular targets and mode-of-action of bioactive natural products
Jan Mart Daluz
I earned my bachelor's and master’s degrees in chemistry, with a focus on natural products, from Mindanao State University - Iligan Institute of Technology in the Philippines. Currently, I am pursuing my PhD Fellowship at Lead Discovery Center GmbH, a translational research company in Dortmund, Germany.
My project within HotBio centers around investigating the targets id and modes- of -action of bioactive marine natural compounds. This is essential because it provides information on how a molecule elicits its pharmacological effect and on which molecular targets and signaling pathways it affects in a disease-relevant model of cancer and infection. I am pursuing these objectives primarily through (phospho)proteomic and genomic approaches, which will then be validated using biophysical, biochemical, and cell-based assays.
Identification of molecular targets and mode-of-action of bioactive natural products
In this project, the molecular targets of bioactive natural products will be elucidated. Various methods can be used, such as affinity chromatography (using the compound of interest bound to a matrix and the protein extract to identify binders; binders will be identified via mass-spec and competition experiments), CETSA assays (= cellular temperature shift assay for the identification of thermally shifted proteins in the presence of compound/modulator), cell painting, crosslinking, functional genetic approaches (e.g. si/sh-RNA-, CRISPR/Cas9-, cDNA- Screens, haploid screening), cellular profiling (e.g. metabolomics, proteomics, gene expression analysis), knowledge-based approaches (e.g. analysis of chemical similarities, machine learning methods, computer-based docking studies). From these methods the most appropriate ones will be applied to elucidate unknown molecular target(s) from known bioactive natural products such as Lulworthinone or MBR-322. In the next step, the most promising natural product candidate identified and profiled within Hotbio will also be investigated with regard to its molecular target, using the previously established methods.
Supervisor: Bert Klebl and Matthias Baumann
Host institution: Lead Discovery Center GmbH
