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

IMIBIC HOSTING OFFER:

La Caixa INPhINIT INCOMING Doctoral Fellowship Programme

GROUP LEADER

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

RESEARCH PROJECT/RESEARCH GROUP

EPIGENETICS AND DNA REPAIR: http://www.uco.es/investiga/grupos/epirep/en/

POSITION 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.

References:

Barbado et al., (2018). Nonenzymatic release of N7-methylguanine channels repair of abasic sites into an AP endonuclease-independent pathway in Arabidopsis. Proc Natl Acad Sci U S A 115, E916-E924.

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.

The biomedical research institute, IMIBIC, located in Cordoba, southern Spain, is a partnership between the University of Cordoba and the Reina Sofia University Hospital. IMIBIC offers a multidisciplinary environment focused on results-oriented research and based on precision medicine and excellence in science. IMIBIC is accredited with the Excellence distinction from the Carlos III Spanish National Institute of Health.

Eligibility Criteria

1) At the call deadline (4^th Feb 2020), 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 2020). 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.

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

Select “IMIBIC – Maimonides Biomedical Research Institute of Cordoba” from the dropdown list under “RESEARCH CENTRE”

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 TITLE".

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://www.lacaixafellowships.org/index.aspx

Schedule:

4 February 2020: Deadline for submitting applications.

18 February 2020: Deadline for submitting the language certificate.

16 April 2020: Notification of the shortlist results.

27 and 28 May 2020: Face-to-face interviews in Barcelona.

2 June 2020: Publication of the final list of selected candidates.

From 2 to 30 June 2020: Matching research centre – fellow.

More Information:

2020 Call for applications:

https://obrasociallacaixa.org/documents/10280/590054/inphinit_incoming_2020_en.pdf/3cfabdbb-9986-df86-f58f-d5289f19672a?t=1572967982849

Web:

https://obrasociallacaixa.org/en/investigacion-y-becas/becas-de-la-caixa/doctorado-inphinit/incoming

Email:

international@imibic.org

ABOUT IMIBIC

IMIBIC, located in Cordoba, southern Spain, is a partnership between the University of Cordoba (UCO) and the Reina Sofia University Hospital. IMIBIC offers a multidisciplinary environment focused on results-oriented research and based on precision medicine and excellence in science. IMIBIC is accredited with the Excellence distinction from the National Institute of Health Carlos III and the “HR Excellence in Research” by the EC.

The Institute is structured in 44 research groups that cooperate in the implementation of five scientific programmes. IMIBIC offers an active environment in which to conduct high-level scientific research. Regular seminars and research events offer the opportunity to meet with national and international experts covering a diverse range of topics in biomedicine. Advanced training of our PhD students is provided primarily through the Doctoral Program in Biomedicine (UCO), hosted at the IMIBIC and integrated by leading scientists from the University and the Hospital. Results from research activities are exposed yearly in the IMIBIC Young Investigator Meetings, providing an ideal environment to strengthen the skills and knowledge of young scientists and to foster translational research by bringing together experimental basic and medical sciences.

IMIBIC is a young and fast-growing research center. It operates in a brand new building located within the UCO Health Sciences Campus and next to the University Hospital. It hosts over 600 researchers and offers the latest technology, equipment, and laboratories to support the technical needs of the research community.

Cordoba is a medium-sized city located in the heart of Andalusia, with excellent transport connections to the main cities of Spain and both to the Mediterranean and Atlantic coasts. Rich in history and culture, Cordoba is a friendly and welcoming city, with a high standard of living, making it an ideal location for international students wishing to carry out their doctoral studies in Spain.