Individual
DC projects

Research project

Investigating the 2-hydrohyglutarate (2-HG) protein interaction network in leukemia cells

Rationale and objectives:

Mutant IDH1/2 drives blood and brain cancers by generating the oncometabolite 2-HG. It is unknown how 2-HGinduced changes of the protein-metabolite network lead to uncontrolled proliferation of cancer cells.

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Thus, we plan:
• To develop structural proteomics methods to analyze nuclear 2-HG and alpha-ketoglutarate (aKG)-protein interactions.
• To combine structural proteomics with metabolomics to quantify 2-HG in the nucleus of leukemia cells.
• To evaluate 2-HG binding sites as druggable target sites screening a library of conventional and epigenetic drugs.

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Envisioned Secondments

UCPH (Zylicz), months 13-14 (2 months) to develop a nucleus-specific degron system for IDH1. EISBACH (Ladurner) months 27-30 (3 months) to carry out a compound screen to modulate novel nuclear targets of 2-HG and aKG.

Recruitment

The estimated annual gross salary for the fellow will be €34.000 (approx.).