Welcome to the Edwards lab!
Thomas A. Edwards, Ph.D.
Astbury Centre for Structural Molecular Biology
School of Molecular and Cellular Biology
Faculty of Biological Sciences,
Office (+44) 113 343 3031
We use Structural Molecular Biology (mainly X-ray crystallography, but including NMR and EM) to study Developmental, Cellular, and Cancer Biology. Projects are based around investigating the structural biology of protein-RNA and protein-protein interactions. Details of specific projects are listed below:
Gene Expression in Single Stranded Negative Sense RNA Viruses:
Bunyavirus nucleocapsid proteins both protect the RNA from degradation in the cell, and interact with proteins such as the RNA dependent RNA polymerase to regulate gene expression and replication. We (collaboration with Dr. John Barr) have solved the crystal structure of N proteins from Crimean Congo Hemorrhagic Fever Virus, Bunyamwera Virus and Schmallenberg Virus, with and without RNA bound. We have used these structures to interpret virus biology, and there is the possibility of anti-viral therapies via structure based drug design.
We are also investigating RNA binding proteins from the human Respiratory Syncytial Virus.
See Tanner et al 2014; Ariza et al 2013; Carter et al 2012. (click publications below).
Translation Control During Embryogenesis:
We are investigating the structural biology of a variety of RNA binding proteins that control translation, splicing, RNA localisation and stability.
Pumilio is a sequence
specific RNA binding protein, and a founder member of the Puf
family of RNA binding domains. We have solved the structure of the Pumilio Puf domain (see Figure, top right) and determined that it
has a novel RNA binding fold. In the developing Drosophila embryo, Pumilio binds to the 3prime UTR of hunchback mRNA and recruits Nanos into a
complex which represses translation. This defines the posterior of the
embryonic anterior-posterior axis. In order to repress translation, the Pumilio:RNA:Nanos complex recruits
another cofactor: Brat (Brain
Tumor). We have also solved the structure of the Brat NHL domain, and proposed
the interaction surface between Pumilio and Brat. We are continuing to
investigate the structure and function of this repression complex using structural and biochemical techniques.
Dazl is a member of the RRM containing DAZ family of RNA binding proteins. Dazl appears to interact with the Pumilio homologue Pum2 in order to control translation of specific mRNAs during differentiation of germ cells; the Dazl:Pum2 complex therefore appears to play a critical role in spermatogenesis. We aim to solve the structure of Dazl in complex with RNA and protein cofactors.
Vts1 is a homolog of Smaug, which represses nanos translation. We have solved the solution structure of Vts1 in complex with RNA by 3D NMR.
SAM68 is a KH domain containing RNA binding protein that regulates alternative splicing of CD44 pre-mRNA changing the binding characteristics of the CD44 cell adhesion molecule. We are using a structural biology approach to investigate the mechanism of regulated splicing.
For examples, see Jenkins et al 2011; Jenkins et al 2009; Gupta et al 2009; Edwards et al 2006; Edwards et al 2003; Edwards et al 2001.