PRR Project

Summary

The selected candidate will be expected to lead a Research Group that matches and reinforces the scientific interests and strategy of the Cancer integrative program of i3S. In that role, he/she is expected to demonstrate strong leadership skills, assemble his/her own team and secure extramural funding for his/her research. The selected candidate must hold a PhD in Health/Life Sciences, or related areas for 12 or more years, an excellent scientific track record, and is expected to pursue highly innovative research projects in frame of the Cancer Integrative Programs. The selected candidate must be experienced in the supervision of PhD and Master students, and willing to contribute to the i3S training mission, by supporting advanced training and participating in graduate and PhD programs. The selected candidate is also expected to carry out duties to which he/she will be elected or appointed in i3S collegiate bodies. Engagement into the i3S educational program and outreach activities is also expected.The mission of the Cancer integrative program at i3S is to translate cutting-edge fundamental science into knowledge and practical benefit for cancer patients. Through major discoveries in fundamental research, the integrative program has established an international reputation in the fields of gastrointestinal, endocrine and breast cancer, hereditary cancer, cancer glycobiology, cancer molecular genetics, cell division and cell cycle control. Reflecting this international status, the integrative program has developed new prognostic, diagnostic and treatment tools by identifying: risk factors and molecular mechanisms that trigger cancer; molecules involved in cell growth and invasion; biomarkers for therapy stratification; and new molecular targets and vehicles for treatment. The Cancer integrative program includes 23 research groups working on molecular and cellular biology, oncobiology, pathology, metabolism, cancer genetics and population genetics, in association with groups working on bioengineering. The groups routinely use cancer cell-lines, organoids, and animal models such as zebrafish, fruit fly and mice, and recur to live imaging, advanced microscopy, high-throughput genomics and proteomics and gene manipulation. All i3S Cancer group leaders conducting translational research in cancer have already attained a secured position. But the Cancer integrative program still needs to strategically guarantee a tenure position to some of the group leaders who are dedicated to unravel the biological mechanisms recognized as cancer hallmarks (such as cell division, chromosome segregation, ageing and gene expression regulation). This basic science branch of the Cancer integrative program has been highly competitive internationally, having attracted most of the 6 ERC grants in i3S and several “la Caixa” research grants, and regularly publishes in top-tier journals like Nature and Science.This Principal Researcher position will be attributed to an outstanding candidate working in the field of Transcriptional Regulation, addressing the impact that non-coding cis-regulatory mutations have in the development of diseases, such as cancer. The inference of the pathogenic impact of the mutations that are present in the original tumors and metastases continues to be a challenge. This inference is still focused on the coding regions, despite genome-wide studies having demonstrated that the majority of disease-associated variants are located in the non-coding genome, and many overlap with chromatin signatures associated to the activity of cis-regulatory elements (CREs) that control gene expression. Similar challenges exist in the identification of risk alleles for the development of cancer and other diseases. An additional level of complexity results from different cell types and tissues having specific arrays of active CREs. Therefore, the tissue specific pathogenicity of a non-coding variant located in a CRE depends on the tissue specific activity of that particular CRE. The Principal Researcher should be proficient in profiling tissue specific active CREs using techniques such as Assay for Transposase-Accessible Chromatin (ATAC-seq) and Chromatin Immunoprecipitation Sequencing (ChIP-Seq), and on the bioinformatic interpretation of data. In order to be able to address the cellular/tissue heterogeneity, expertise in Fluorescence-Activated Cell Sorting (FACS) or in single-cell sequencing technologies is expected. Aiming at proving the functional impact of the non-coding variants, proficiency in in vivo and in vitro reporter assays and targeted mutagenesis methods is required, and in its phenotypic validation via in vivo models.