Call for PhD Fellow position interested in applying for MSCA DN in Hub Molecules of Metabolism and Signalling -Key regulators of Life (HubMOL DC7)

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In the context of the European Horizon funded Marie Skłodowska-Curie Actions - doctoral network HubMOL - Hub Molecules of Metabolism and Signalling – Key regulators of Life we have 16 PhD positions available at 10 different research institutions and 4 companies across Europe. HubMOL brings together internationally leading academic and industrial expertise in epigenetics, mathematical modelling and high-resolution stable isotope labelling based analysis of the dynamics of metabolic cofactors and post translational modifications (PTMs) and will use advanced in vitro and animal models for translational studies to develop knowledge based nutritional intervention strategies for hub molecules. The hub molecules of life that include ATP (adenosine triphosphate), NAD (nicotinamide adenine dinucleotide), CoA (coenzyme A), FAD (flavine adenine dinucleotide) and SAM (S-adenosylmethionine), comprise a set of cofactors that are crucial for all cellular functions. More information can be found at the project website: www.hubmol.eu Subproject 7 with employment at Eisbach Bio Munich, Germany https://www.eisbach.bio/ EISBACH BIO GmbH is a biotechnology company based in Planegg, near Munich, Germany. It specializes in drug discovery and development, particularly targeting chromatin remodeling enzymes and synthetic lethality pathways for cancer therapy. The company leverages its molecular expertise in epigenetics and genome stability to develop innovative small-molecule inhibitors that target specific vulnerabilities in cancer cells. Its platform addresses the inhibiton of target enzymes using allosteric approaches that hit the unique activation mechanisms that underlie the regulation of the molecular machines that the company focuses on. In doing so, EISBACH’s speerheads the development of first-in-class, next-generation precision oncology treatments. EISBACH BIO collaborates with research institutions and pharmaceutical companies to advance its pipeline of drug candidates, the first of which has entered clinical Phase I/II testing at the MD Anderson Cancer Center in Houston, TX (USA). Eisbach Bio GmbH focuses on pioneering precision oncology through the development of allosteric drugs that target molecular machines essential for tumor genome reorganization. Utilizing our proprietary ALLOS platform, we identify and exploit the genetic vulnerabilities of cancer cells by targeting the unique molecular vulnerabilities of our target enzymes, notably the allosteric sites that we identify, validate and target using small molecule drug candidates. Eisbach's research encompasses nucleosome remodeling enzymes, DNA-dependent nuclear helicases as well as nuclear PARP family enzymes, all of which are critical for efficient DNA repair and chromatin reorganization. Our allosteric approach aims to create safe, orally bioavailable first-in-class or best-in-class anti-tumor therapies that induce synthetic lethality in cancer cells, halting tumor growth while minimizing damage to healthy cells, thus significantly reducing side-effects. Our lead candidate includes a small molecule inhibitor of ALC1, an important molecular machine that reorganizes the genome upon DNA damage, which has entered clinical Phase I/II trials in the autumn 2024. Synergy between HPF1-mediated serine ADP-ribosylation of chromatin and ALC1 chromatin remodeller function in the DNA damage mediated and NAD-dependent activation of the nuclear enzymes PARP1/2. Background: The conversion of the metabolite NAD into poly-(ADP-ribose) (PAR) during DNA damage is crucial in cancer. PARP1/2 inhibitors are clinically useful but have toxicity and resistance issues. HPF1 completely alters PARylation's target amino acid in the DNA damage response, yet its potential as a cancer target remains underexplored . Objectives: (1) Dissect the functions and biological roles of ALC1 and HPF1 in PARP1/2-mediated DNA damage responses; (2) Determine the role of HPF1 in the NAD-dependent and poly-(ADP-ribose)-med