A Molecular Magnifying Glass to Dissect the Interaction Between Cancer and Host

Every cell in our body displays on the surface sugars, so-called glycans, that are linked to other biomolecules such as proteins. When a cell turns into a cancer cell, it displays different types of glycoproteins that help the cancer survive. Some of the current biomarkers used by the NHS to detect cancer are proteins that contain very high amounts of glycans. While cancer glycoproteins have outstanding clinical potential for both diagnosis and therapy, it is very challenging to distinguish them from native glycoproteins from the host by methods of biology alone. Through ground-breaking new developments in our groups (Nat. Commun. 2022; J. Proteom. 2021; Nature 2019;) the tools are finally within reach to accurately profile cancer-derived glycoproteins and understand how they change during tumorigenesis, for instance when surrounded by host-derived cells or in metastasis.

In this studentship, you will apply innovative tools in ex vivo cell biology (Cancer Lett. 2022; Nat. Protoc. 2020), chemical biology (Nat. Commun. 2022; Curr. Opin. Chem. Biol. 2021) and mass spectrometry (glyco-)proteomics (J. Proteom. 2018; Dis. Model and Mech. 2020; J. Amer. Soc. Mass Spectrom. 2021) to study the glycoproteins specifically produced by breast cancer cells, and their role in disease formation. In close collaboration with members of all three groups, you will use these tools to understand how the presence of host cells "shapes" the signature of these glycoproteins. The project builds on prior work of all three labs and will focus on ex vivo tissue co-culture as well as mass spectrometry glycoproteome analysis.

This project will be based at the Francis Crick Institute, a flagship of biomedical science with outstanding strong support in all aspects of research including a state-of-the-art Proteomics Science Technology Platform (STP). At the Crick, you will be jointly supervised by Dr. Ben Schumann and Dr. Ilaria Malanchi, with close relationships with the lab of Dr. Paul Huang at the top-tier Institute of Cancer Research. You will work with lab members of all three groups as well as the STPs. We are looking for candidates with an excellent background in biology, biochemistry, chemical biology or related fields. Experience in mammalian cell culture and/or mass spectrometry proteomics is desirable, with training opportunities in a highly supportive environment. We put heavy emphasis on strong communication skills, collegiality, scientific integrity and mindfulness of all aspects of health and safety. You will be integrated in the Institute of Chemical Biology PhD programme at the Imperial College Chemistry Department of Chemistry, featuring outstanding support, regular progress reports and assessments. This project requires no experience or background in synthetic chemistry. Please note that this project might require working with cells or tissues derived from laboratory animals. Direct animal work is not required.

References:
Calle et al., J. Amer. Soc. Mass Spectrom. 32, 2021.
Cioce et al., Nat. Commun. 13, 2022.
Cioce et al., Curr. Opin. Chem. Biol. 60, 2021.
Krasny et al., J. Proteom. 189, 2018.
Krasny et al., Dis. Model and Mech. 13, 2020.
Milighetti et al., J. Proteom. 241, 2021.
Ombrato et al., Nature 572, 2019.
Ombrato et al., Nat. Protoc. 16, 2020.
Rosell et al., Cancer Lett. 544, 2022.