Our research aims to understand how the ubiquitin system contributes to innate immune signalling triggered by bacterial pathogens and cytokines, with a particular focus on the signalling properties of ubiquitin and how ubiquitin regulates NF-kB-dependent transcriptional responses, inflammation and cancer.
Chronic or unresolved inflammation is an enabling characteristic of cancer and infections are estimated to account for 1 in 6 of all malignancies. Understanding the basic regulatory mechanisms controlling innate immune signalling, such as ubiquitination, will contribute to a molecular understanding not only of immune-related disorders but also of the interplay between inflammation and cancer, and has the potential to reveal molecular targets for novel treatment strategies.
Ubiquitin can be assembled in eight different ways by the ubiquitin system to create different types of ubiquitin chains. Several of these contribute to innate immune signalling and inflammatory responses, but the role and regulation of most ubiquitin chain types - collectively termed atypical ubiquitin chains - remain poorly understood. Research in our group aims to uncover how the ubiquitin system regulates these processes, with a particular focus on the signalling property of ubiquitin.
Key questions we are addressing include:
How is the Met1-linked ubiquitin conjugating machinery regulated?
Met1-linked ubiquitin is assembled by the Linear UBiquitin chain Assembly Complex (LUBAC) and has a key role in facilitating immune signalling. We are interesting in understanding how LUBAC function is regulated in the cell.
What is the function of atypical ubiquitin chains in inflammatory signalling?
We are exploring the role of these poorly characterized ubiquitin chain types in signalling. As part of this, we are developing methods to study individual chain types biochemically and functionally.
How does ubiquitin signalling influence inflammatory responses to infection and cancer?
We want to understand how ubiquitin signalling affects inflammation and the immune defence against bacterial infections and how these processes impinge on early stages of cancer development.