The Gebauer group focuses on understanding translational reprogramming of cancer cells. This non-genomic mechanism of cancer cell adaptation allows rapid responses to a variety of stress conditions and contributes to cell malignancy.
We are particularly interested on RNA-binding proteins (RBPs), which targets they recognize, how these targets are regulated, and how RBPs themselves are modulated to coordinate post-transcriptional gene expression. We have recently performed an unbiased screen to identify RBPs with roles in melanoma progression, and currently focus on several of them, including unconventional RBPs with roles in the unfolded protein response (a fundamental stress response necessary for the survival of cancer cells), or more classical RBPs with ill-defined functions.
We use high-throughput methods combined with bioinformatics, biochemistry, cell-based assays and animal models to understand fundamental principles of RBP function. We aim to capitalize on the generated knowledge to identify reliable biomarkers and design therapeutics with high specificity.
Merits of the lab:
Our group has >20 years of experience in the RNA field, working on the subject of translational control during embryonic development and cancer.
Latest achievements include uncovering new modes of RNA recognition by RBPs (Nature 2014, Cell Reports 2020), identifying RBPs that function as oncogenes in melanoma and dissecting the underlying mechanisms (Cancer Cell 2016, Oncogene 2021), and uncovering context specific functions for RBPs in cancer (Cell Reports 2022).
We have trained 13 PhD students and 8 postdocs, many of which have moved into leadership positions in academia or industry.
Why do we want medical doctors?
We have trained a medical doctor supported by a PhD4MD fellowship. This doctor is now an oncologist in charge of clinical trials at Hospital Clinic, and we remain collaborating with him. In addition, we have established network of clinicians that help us assess the clinical potential of our findings.
The student will participate in ongoing efforts to understand the role of RNA-binding proteins in melanoma progression. The specific subject will be decided together with the student according to his/her affinities. Examples include developing and optimizing methods to assess RNA-protein interactions in tissue samples, understanding the relevance of RBP isoforms in cell differentiation, stemness and cancer, or reverse translational approaches where findings from our current clinical studies dictate hypotheses to be checked in the lab.
How we will do it?
The student may use a variety of technologies, including high-throughput assays (iCLIP, RNA-Seq, RIC, SILAC, ribosome profiling), molecular (Western blot, IP, quantitative PCR, 2D-PAGE, transfections, infections) and cell-based approaches (anoikis resistance, 2D and 3D growth, invasion, clonogenicity), as well as microscopy in order to understand the function of RBPs.
Why is this important?
This research is important because, despite representing one of the major protein families in the cell, RBPs are a relatively uncharted field in cancer biology, and represent a source of novel biomarkers and therapeutic targets. Studying RBPs involved in stress response and resilience of cancer cells to external challenges may uncover novel vulnerabilities that could be targeted for therapeutic intervention.
Who is a good fit for the project?
Experience in medical oncology and a strong interest in understanding molecular mechanisms of gene regulation. Experience on the bench and in exploring databases. Interest in bioinformatics is desirable.
IDIBAPS#1 – Developing and investigating computing, machine learning and physiological modelling for understanding each individual heart towards personalised medicineDavid Brena2022-05-17T10:37:53+00:00