La Caixa INPhINIT INCOMING Doctoral Fellowships: DNA REPAIR OF ABASIC SITES INDUCED BY ANTITUMORAL ALKYLATING AGENTS IN CANCER CELLS

IMIBIC HOSTING OFFER:

La Caixa INPhINIT INCOMING Doctoral Fellowship Programme Call 2021

GROUP LEADER

Prof. Teresa Roldán-Arjona (ge2roarm@uco.es)

RESEARCH PROJECT/RESEARCH GROUP

EPIGENETICS AND DNA REPAIR

POSITION DESCRIPTION

Research Project / Research Group Description

Therapeutically-induced DNA damage remains a major strategy in cancer treatment, but the ability of tumor cells to repair DNA lesions impacts its efficacy. A basic understanding of DNA repair mechanisms used by cells to repair DNA lesions is essential to rationally design appropriate combinations of antitumoral agents and DNA repair inhibitors. Temozolomide (TMZ) and other DNA alkylating drugs with clinical relevance induce N7-methylguanine (N7-meG), which undergoes depurination and generates abasic (apurinic/apyrimidinic, AP) sites in DNA. AP sites may be processed by AP endonucleases or AP lyases, but the relative roles of both types of enzymes are poorly understood. We have recently reported that the model plant Arabidopsis uses an AP lyase-dependent pathway to repair AP sites generated by spontaneous loss of N7-meG (Barbado et al., 2018). In this pathway, AP site incision is catalyzed by the AP lyase FPG, which generates as intermediate a single-nucleotide gap with a 3'-phosphate terminus that is processed by the DNA 3'-phosphatase ZDP before repair is completed.

Importantly, human cells possess two FPG homologs (NEIL1 and NEIL2) and a ZPD homolog (PNK). However, the relevance of such enzymes in the repair of AP sites generated by DNA alkylating agents remains unexplored. In this project, we will use a combination of genetic and biochemical approaches to test the hypothesis that a NEILs/PNK repair pathway mediates resistance of human cells to TMZ and other antitumoral drugs. If the hypothesis is confirmed, AP lyases NEIL1/2 and the DNA phosphatase PNK might become attractive targets for pharmacological inhibition in order to potentiate cancer treatments. Results may also shed light on the mechanisms of TMZ resistance exhibited by numerous tumors and could help to identify potential genetic variants that influence response to chemotherapy.

Job position description

The 2015 Chemistry Nobel prize awarded to DNA repair studies recognized the prominent role of this field in the fight against human disease, and research in this area will certainly pave the way for future cancer therapies. The applicant will work at the cross-roads of basic and applied research related to cancer and DNA repair, and he/she will be in an optimum position to choose in the future among different career paths, either in academic or non-academic sectors. Opportunities related to technologies, diagnostics and medicines are growing steadily and will facilitate cross-sector mobility of researchers working in this area.

The applicant will develop new knowledge in key DNA repair mechanisms, and their relevance for human disease. He/she will also acquire training in research skills in diverse disciplines, such as Biochemistry, Genetics, Cellular and Cancer Biology, in addition to DNA repair. The training through research will be complemented by practicing skills relevant for the development of an independent research career, such as achieving original, independent and critical thinking, learn how to give successful oral presentations and learn how to write scientific papers.

IMIBIC will ensure the effective integration of the researcher in the institute and will facilitate his/her participation in all activities that are beneficial for training and career development, including in-house courses, seminars and symposia. The researcher will work in the multidisciplinary environment offered by the institute, which facilitates and promotes collaboration between the different fields of biomedical research. Advanced training of our PhD students is further provided through the Doctoral Program in Biomedicine of the University of Cordoba, hosted at the IMIBIC and integrated by leading scientists from the University and the Reina Sofia University Hospital.

How to Search for this offer:

You can find this offer via the Offer Finder, available at https://finder.lacaixafellowships.org/finder

Select “IMIBIC – Maimonides Biomedical Research Institute to Cordoba” from the dropdown list under “HOST ORGANIZATION”

You can also search the position by its title "DNA REPAIR OF ABASIC SITES INDUCED BY ANTITUMORAL ALKYLATING AGENTS IN CANCER CELLS" under "Search by project title / Job position / Positions description”

Eligibility Criteria

1) At the call deadline (4^th Feb 2021), applicants must be in the first four years (full-time equivalent research experience) of their research careers and not yet have been awarded a doctoral degree.

2) At the time of recruitment, candidates must comply with one of the following options:

• To have completed the studies that lead to an official university degree adapted to the European Higher Education Area awarding 300 ECTS credits, of which at least 60 ECTS credits must correspond to master level.
• To have completed a degree in university not adapted to the European Higher Education Area that gives access to doctoral studies. The verification of an equivalent level of studies to the ones mentioned above will be made by the university when the admission procedure starts.

3) Candidates must not have resided or have carried out their main activity (work, studies, etc.) in Spain for more than 12 months in the 3 years immediately prior to the call deadline (4^th Feb 2021). Short stays, such as holidays, done in a country other than their country of usual residence (where they carried out their main activity), will be considered as time spent in their country of usual residence.

4) Candidates must have a demonstrable level of English (B2 or higher).

5) Only candidates whose applications meet all the requirements of the call may be accepted.

How to Apply:

If you want to apply for an INPhINIT fellowship, click on the link below to create your personal account and fill in the on-line application form: https://candidate.lacaixafellowships.org/login

Schedule:

4 February 2021: Application deadline.

18 February 2021: Deadline for submitting the language certificate.

22 April 2021: Notification of the shortlist results.

25, 26 and 27 May 2021: Face-to-face interviews in Barcelona.

7 June 2021: Publication of the final list of selected candidates.

7 – 30 June 2021: Matching between the research centres – fellows.

More Information:

Call for application:

https://fundacionlacaixa.org/es/becas-la-caixa-doctorado-inphinit-incoming

Programme Rules:

https://fundacionlacaixa.org/documents/10280/162494/programme-rules-inph...

Email (for questions concerning the host organisation IMIBIC):

international@imibic.org