Exploring the divergent properties of E3 ubiquitin ligases using cellular and biochemical approaches

Key information

Application close date
07 February 2023, 11:59 GMT
Hours per week
36 (full time)
Application guidance
Posted 22 December 2022

Research topics

Biochemistry & Proteomics Cell Biology Imaging Infectious Disease Structural Biology & Biophysics
Background texture taken from the lab imagery.

This is a summer student position supervised by Jane Dudley from Katrin Rittinger's lab. 

Introduction to the Science

The addition of ubiquitin to substrates can result in a wide variety of cellular outcomes, from triggering signalling cascades to inducing protein degradation. Ubiquitination must be tightly controlled to prevent over- or under-stimulation of these pathways, and dysregulation of the ubiquitin system is linked to many diseases. However, much still remains unknown about how ubiquitination is so precisely regulated to maintain homeostasis in diverse cell types in our bodies.

About the Project

The tripartite motif (TRIM) family is a group of proteins that share a conserved domain structure that contains a RING domain, which is capable of catalysing the addition of ubiquitin to targets. However, our work has revealed that, despite striking similarities in amino acid sequence, not all family members seem to be capable of this ubiquitination activity in vitro [1]. Understanding the true function and regulation of TRIM proteins is important as many of them have been implicated in a variety of diseases, such as cancer and neurodegeneration [2].

This project will investigate the differences between TRIM family members to identify those that have E3 ligase activity and those that may fulfil other functions. The key to unlocking this puzzle may lie in aligning cellular and biochemical data under different conditions. For example, these proteins may only become active in specific cellular contexts, such as infection or proteotoxic stress. The successful candidate will address this problem by gaining experience in molecular biology, biochemical assays, mammalian cell culture, ELISA assays, western blotting, and confocal microscopy.

About You

This project would be suitable for a candidate undertaking a degree in biochemistry, cellular and molecular biology, or similar, and has an interest in investigating how protein ubiquitination plays a role in cellular function.

References

1.         Fiorentini, F., Esposito, D. and Rittinger, K. (2020)

            Does it take two to tango? RING domain self-association and activity in TRIM E3 ubiquitin ligases.

            Biochemical Society Transactions 48: 2615-2624. PubMed abstract

2.         Hatakeyama, S. (2017)

            TRIM family proteins: Roles in autophagy, immunity, and carcinogenesis.

            Trends in Biochemical Sciences 42: 297-311. PubMed abstract