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Mr Richard Timms

Mr Richard Timms

Cellular immune response and immune regulation

Immunity and host defences


Office Phone: 01223 762629

Research Interests

I am interested in using novel genetic technologies coupled with the power of next-generation sequencing to identify functions for novel genes involved in cellular processes.

 

Working in the laboratory of Professor Paul Lehner, I have spent my doctoral research performing non-lethal forward genetic screens in the near-haploid KBM7 cell line. Such screens are a powerful technique to examine gene function in human cells, and are readily adaptable to the study of essentially any cellular process. This work has assigned functions to two poorly characterised genes, PLP2 and TMEM129, which are hijacked by viral proteins that interfere with antigen presentation by MHC-I molecules. More recently we have used this approach to identify a novel component of the epigenetic silencing machinery – the HUSH complex - which is responsible for heterochromatin maintenance in human cells, and which could be important in the context of viral latency.

 

The rapid recent development of CRISPR/Cas9 technology offers an alternative method to carry out forward genetic screens in human cells. The focus of my current work is to utilise the power of haploid and CRISPR screens to identify further novel genes involved in chromatin regulation.

Keywords

forward genetic screens ; CRISPR/Cas9 ; HUSH complex ; near-haploid human KBM7 cells ; next-generation sequencing

Key Publications

Timms RT*, Tchasovnikarova IA*, Matheson NJ, Wals K, Antrobus R, Göttgens B, Dougan G, Dawson MA, Lehner PJ (2015) Epigenetic silencing by the HUSH complex mediates position-effect variegation in human cells. Science 348: 1481-1485

 

van den Boomen D, Timms RT, Grice GL, Stagg HR, Skjødt K, Dougan G, Nathan JA, Lehner PJ (2014) TMEM129 is a Derlin-1 associated ERAD E3 ligase essential for virus-induced degradation of MHC-I. Proc. Natl. Acad. Sci. USA 111: 11425-11430

 

Timms RT, Duncan LM, Tchasovnikarova IA, Antrobus R, Dougan G, Weekes MP, Lehner PJ (2013) Haploid genetic screens identify an essential role for PLP2 in the downregulation of novel plasma membrane targets by viral E3 ubiquitin ligases. PLoS Pathogens 9(11): e1003772

 

Timms RT*, Duncan LM*, Zavodszky E, Cano F, Dougan G, Randow F, Lehner PJ (2012) Fluorescence-based phenotypic selection allows forward genetic screens in haploid human cells. PLoS ONE 7(6): e39651

 

*equal contribution