Position 12

Role of Interferon and of ISG15 system in DNA replication.

PhD position in ‘Role of interferon/ISG15 system in genome stability and drug response’ at the group of Prof Lorenza Penengo in the Institute of Molecular Cancer Research at the University of Zurich, Switzerland.

What is the candidate going to do?

Interferons (IFNs) comprise a large family of cytokines that have been extensively studied in the context of viral and bacterial infections, but that are also important players in the crosstalk between tumour cells and immune cells as key drivers of inflammation. In addition to their immune-stimulatory effects, which are exploited in cancer therapy, IFNs may also trigger immune-suppressive responses, revealing an important mechanism used by cancer cells to promote malignant progression and resist therapies.

Despite their relevance in tumour microenvironment as well as in therapeutic regimens, still little is known on the effects of IFNs on the surrounding cells and tissues. The present project lays on this context. The student will assess the effect of IFN treatment on important processes, such as DNA replication, and investigate how the upregulation of the IFN system impacts on the response of cancer cells to chemotherapy. We already collected key data showing that the activation of the IFN system, via the upregulation of the ubiquitin-like modifier ISG15, has a major impact on the stability of nascent DNA. This effect is particularly dramatic in specific genetic contexts where genome stability is undermined by mutations in tumour suppressor genes.

A key part of the project will be to combine mass spectrometry analysis, to identify potential candidates involved in this regulation, with data derived from CRISPR-based genomic screening, which will be carried out during the student’s secondment to another laboratory that is part of the network. The goal is to identify factor/s and mechanism/s responsible for the aberrant DNA replication induced by ISG15 and investigate the potential of ISG15 deregulation/inactivation as a sensitizing factor in combination with commonly used anti-cancer drugs.

What does the candidate have to offer?
  • MSc in Biology (Molecular Biology, Biochemistry), Biomedicine or similar disciplines
  • Genuine motivation to understand the mechanisms of cancer development
  • Strong technical skills and scientific knowledge
  • Propensity for teamwork

Preference will be given to candidates with experience in CRISPR-mediated gene editing, mass spectrometry, data analysis, organoids culturing.

About the institution

The University of Zurich (UZH) is one of the Europe’s most prestigious research institution and also Switzerland’s largest university. Penengo’s laboratory is located at the Institute of Molecular Cancer Research (IMCR), which is affiliated to the Faculty of Medicine and the Faculty of Science at the University of Zurich (UZH). The IMCR is a world-renowned centre dedicated to genome stability. The main research emphasis is on how different types of genomic stress lead to cancer pathogenesis and how they can alter the course of the disease by targeting certain anti-cancer chemotherapeutics. At the IMCR the student will be exposed to a stimulating atmosphere and an international scientific environment and will participate in scientific discussions during meetings and journal clubs.

Any questions?

Do you have any questions or do you require additional information? Please contact: Prof Penengo. Email: penengo@imcr.uzh.ch.