PhD position in Computational Biology - Center for Genomic Science, Milan (Italy)

Posted on June 29,

Applications are now open for one PhD position in Computational Biology (https://www.semm.it/content/transcriptional-and-epigenetic-mechanisms-provided-noncoding-rnas-human-cancer-nicassio) in the Non-coding Genome Group at the Center for Genomic Science of [email protected] ([email protected]), Milan (Italy) to study transcriptional and epigenetic mechanisms provided by noncoding RNAs in human cancer.

Host institution
The [email protected] (https://www.iit.it/it/cgs-semm) is an outstation of the Italian Institute of Technology (IIT) and its scientific mission is the acquisition, development, and application of genomic technologies towards a better understanding of complex biological processes and diseases in humans, with an emphasis on cancer. Being located on the research campus that IFOM (FIRC Institute of Molecular Oncology) and IEO (European Institute of Oncology) jointly founded twenty years ago, [email protected] is immersed in an environment that is highly conducive to basic and translation research in cancer. The Center also partakes in the RNA initiative (https://www.iit.it/web/irna), a scientific action promoted by the IIT and aimed at generating ground-breaking interdisciplinary knowledge in the fields of RNA biology, RNA technologies and RNA-based therapeutics.

Hosting lab
The Noncoding Genome Group, headed by Dr Francesco Nicassio (https://www.iit.it/people-details/-/people/francesco-nicassio), studies the function and regulation of non-coding transcripts (microRNAs and long non-coding RNAs), with a particular emphasis on how regulatory RNAs shape the identity and properties of mammalian cells in cancer stem cells and during cancer evolution (therapy resistance, metastatic spread).

Project details
We use cutting-edge genomic approaches to achieve a high-resolution characterization of the transcriptional/epigenetic landscape of cancer cells, focusing on their evolutionary trajectories in time and space. Indeed, the spatial and temporal heterogeneity characterizing cancer usually represents a major hurdle to both basic and translation research. Within the same tumor, cancer cells can behave differently with some of them acquiring the ability to adapt in response to harsh or even hostile conditions, produced either by the host or following cancer treatment. In recent years, it has become increasingly evident that non-coding mechanisms play an important role in gene regulation. Short (microRNAs) and long non-coding RNAs (lncRNAs) as well as non-coding DNA elements (enhancer, silencer), have emerged as key elements in the adaptive response mechanisms and in the transcriptional/epigenetic reprogramming of cancer cells, which occur during cancer evolution and in the most aggressive cases of the disease, such as metastatic spread or tolerance/resistance to therapy. These RNA elements are also extremely interesting in applied medicine, as they could be exploited to provide a new generation of targets for therapeutic/theranostic applications with unprecedented sensitivity and specificity.

The successful PhD candidate will be working on a highly interdisciplinary project, in which stroma-enhancing cancer organoids, a sort of "cancer avatars", able to mimic the 3D spatial tissue organization and maintain the genetic and phenotypic heterogeneity of their tissue of origin will be used as model systems. Cutting-edge approaches, including state-of-the-art genomic platforms (i.e. RNAseq, ATACseq, DNAseq, Genomic Barcoding, Single-Cell sequencing), genetic interrogation by multiplexed CRISPR/cas9 system (CRISPRi/a, CROP-seq, Perturb-seq approaches) and novel emerging methodologies that will be developed as part of the project (e.g. Spatially-resolved omics) will be applied to the investigation of the role noncoding RNAs and DNA elements play in the adaptive response of breast cancer cells following anticancer therapies and in the context of advanced 3D models and primary tumor organoids. The final aim of the project is to gain insight into the genetic and epigenetic factors that hinder the success of established anticancer therapies.

Interested applicants should apply via the European School of Molecular Medicine (4d-semm.ieo.eu:8083/PhD2021/index.php)

Application closing date: 19 July 2021
Exam dates: 3 Sep (online written test), 6-10 Sep 2021 (online interviews)
PhD Course starting date: 1 Oct 2021

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