PhD Positions

(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)-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

Where to apply

E-mail: careers@eisbach.bio

Requirements

Research Field: Biological sciences

Education Level: Master Degree or equivalent

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.

Languages: English

Level: Excellent

Research Field: Biological sciences

Additional Information

Eligibility criteria

Mobility rule:

Researchers can be of any nationality, but they are required to undertake physical, transnational mobility (i.e., move from one country to another) when taking up their appointment.

Additionally, researchers shall not have resided or carried out their main activity in the country of their host organization for more than 12 months in the 3 years immediately prior to the reference date.

Researchers who are refugees in an EU Member State or a Horizon Europe Associated Country according to the Geneva Convention are exempted from the mobility rules above if they fulfill the other eligibility conditions.

Doctoral Candidates (DCs) rule:

Applicants must be doctoral candidates, i.e. not already in possession of a doctoral degree at the date of the recruitment. Researchers who have successfully defended their doctoral thesis but who have not yet formally been awarded the doctoral degree will not be considered eligible. See Article 6.2.A (b) (i) of the HE unit model grant agreement.

Applicants must meet the admission requirements of the doctorate degree program of the hiring institutions for each position.

Selection process

The applicants will be assessed by an expert committee. The committee's mandate is to undertake an assessment of the applicants' qualifications based on the written material presented by the applicants, and the detailed description draw up for the positions.

The applicants who are assessed as best qualified will be called to an interview. There will be a two-stage interview process. The interview should among other things, aim to clarify the applicant’s motivation and personal suitability for the position.