La Caixa INPhINIT INCOMING Doctoral Fellowship Programme: CRISPR-MEDIATED EPIGENETIC EDITING 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

Aberrant DNA methylation is frequent in human cancers, which usually display hypermethylation and silencing of tumor suppressor genes. Active DNA demethylation mechanisms may be exploited to reverse epigenetic silencing in tumors, but they are still poorly understood in human cells. A clearer picture is available from plants, which have evolved a family of DNA glycosylases that initiate demethylation through a Base Excision Repair (BER) mechanism. Structural and functional analysis, mostly performed by the host group, has identified the main molecular features of the prototypic plant DNA demethylases ROS1 and DME. Overexpression of DME in colon cancer cells reactivates hypermethylated silenced loci and partially restores the methylation pattern observed in normal tissue (Morales-Ruiz et al., 2018). We have also shown that a fusion protein containing the catalytic domain of ROS1 and the DNA binding domain of yeast GAL4 specifically demethylates and reactivates a methylation-silenced reporter gene in human cells (Parrilla-Doblas et al., 2017). The field of Epigenetic Editing is undergoing a revolution with the advent of RNA-programmable CRISPR-Cas9 technology, which relies on the CRISPR-associated protein Cas9, an endonuclease that uses an RNA as a guide sequence (gRNA) to form base pairs with DNA target sequences and introduce site-specific double-strand breaks at target locations. Proteins fused to catalytically inactive or “dead” Cas9 (dCas9) can be recruited by gRNAs to specific target DNA sites. The research project aims to develop an RNA-programmable dCas9-ROS1-based DNA demethylation system for targeted reactivation of silenced genes in tumor cells.

References:

Morales-Ruiz et al. (2018). DNA methylation reprogramming of human cancer cells by expression of a plant 5-methylcytosine DNA glycosylase. Epigenetics 13, 95-107.

Parrilla-Doblas et al. (2017). Targeted DNA demethylation in human cells by fusion of a plant 5-methylcytosine DNA glycosylase to a sequence-specific DNA binding domain. Epigenetics 12, 296-303.

Job position description:

Epigenetic research in cancer has gained momentum in the last 10 years, and the flux of new data is expanding a field on which many expectations are placed. Working at the cross-roads of basic and applied research related to cancer epigenetics, the applicant will be in an optimum position to choose in the future among different career paths, either in academic or non-academic sectors. Epigenetic therapies are a new frontier in the fight against human disease, and opportunities related to epigenetic technologies, diagnostics and medicines are growing steadily and facilitate cross-sector mobility of researchers working in this area.

The applicant will develop new knowledge in key epigenetic 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 Epigenetics. 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 "CRISPR-MEDIATED EPIGENETIC EDITING 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.