Responsibilities
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)-mediated recruitment of ALC1 chromatin remodeller to DNA damage sites; (3) Establish the mechanism of PARP inhibitor sensitization mediated by ALC1 and HPF1 in isolation and together.
Supervisor: Andreas Ladurner : andreas@eisbach.bio Link to DC7: HubMOL | UiT
Gross salary: Annual gross salary: 42.000 EUR, Family allowance yearly: +7.200 EUR if applicable
Your Expertise
Skills/Qualifications
A master in biochemistry, cell biology, biomedicine, analytical chemistry (subprojects 1,2,5,8, 9,15) or bioinformatics with good understanding of biochemistry (subprojects 2,5,9)
Proven prior knowledge in hub molecule relevant topics
A high level of motivation and interest for topics of HubMOL
High-level of collaborative and communicative skills
Relevant expertise in cell metabolism and fields related to the HubMOL projects
Excellent level of English speaking and writing skills (required).
Specific Requirements
We are seeking a highly motivated candidate with:
Academic Background:A Master’s degree (or equivalent) in Molecular Biology, Cell Biology, Cancer Biology, Biochemistry, Biophysics, or related fields.
Research Experience:Experience in chromatin biology, DNA damage repair, or epigenetics.
Experience with techniques such as protein expression/purification, CRISPR/Cas9 gene editing, and advanced microscopy is highly desirable.
Technical Skills:Proficiency in molecular cloning, cell culture, and biochemical assays.
Familiarity with omics-based approaches (e.g., proteomics, transcriptomics) is a plus.
Soft Skills:Strong analytical and problem-solving abilities.
Aptitude for teamwork
Effective written and oral communication skills in English.
Language Skills:Fluency in English is required
Motivation: A passion for precision oncology and a drive to explore the therapeutic potential of novel drug targets will be critical for success in this role.
Please read more details on https://euraxess.ec.europa.eu/jobs/459788
To apply, please send your application documents as per guidelines (https://euraxess.ec.europa.eu/jobs/459788) to the following email:
Why Eisbach
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.