... understanding life in molecular detail

Dr Thomas Edwards

  RNA Binding Proteins & Structural Molecular Biology


We use Structural Molecular Biology (mainly X-ray crystallography, but including NMR and EM) to study Developmental & Cellular Biology, Microbiology, and Cancer.

Current major projects include:
  • RBPs & N proteins from -ve sense RNA viruses
  • protein-protein interactions and their inhibition
  • mechanisms of antibiotic resistance
  • Pumilio, Dazl, axis specification & fertility

The Edwards lab uses high resolution structural biology techniques to address a range of biological questions:

            Localisation of mRNA in the egg and early embryo drives early developmental decisions and fates such as axis specification during Drosophila embryogenesis. The protein Pumilio along with cofactors Nanos and Brat repress hunchback translation in the posterior to set up the a-p axis. We have solved the crystal sstructure of fly Pumilio, and extended this work into mammals with ethe structure of mouse Pum2. An additional Pumilio binding protein in mammals, Daz-like (Dazl) is also an RNA binding protein and a major determinant of human male fertility. We have solved the crystals structiure of Dazl bound to various RNA sequences and defined a new Dazl binding consensus sequence. In addition, the mRNA is localised by molecular motors, leading us to study the structure of dynein and myosin (in collaboration with Astbury members Stan Burgess, Michelle Peckham and Peter Knight) by EM, and domains by crystallography.

            Many of the processes described above are driven by protein-protein interactions (PPIs). In collaboration with Andy Wilson’s group in Chemisty and Astbury, we are attempting to design and synthesis novel inhibitors of helix mediated PPIs important in apoptosis and cancer.

            In collaboration with John Barr, we are investigating the structure and function of nucleocapsid proteins from RNA virus such as Crimean-Congo hemorrhagic fever virus, Shmallenberg virus and Bunyamwera virus. These proteins encapsidated the genomic RNA into ribonucleoprotein (RNP) assemblies to protect it and also interact with other virla proteins such as the polymerase and membrane glycoproteins. We have also used EM (with Neil Ranson), and Mass Spec (with Alison Ashcroft and Nic Stonehouse), to study RNP assembly.

            In collaboration with Alex O’Neill, we are investigating the mechanism of antibiotic resistance via the crystal structures of resistance proteins such as FusB/FusC.

Detailed research programme                  Close ▲
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Associate Professor
BSc (Bath) PhD (Bath)


PhD University of Bath 1996
post-doc , Mt Sinai Med School, New York 1997-2002
Research Assistant Professor, Mt Sinai Med School, New York 2002-2005
Lecturer (Leeds) 2005-2012

Garstang 8.53d
School of Molecular and Cellular Biology
0113 343 3031
t.a.edwards@leeds.ac.uk
http://www.fbs.leeds.ac.uk/staff/tae/

Selected Publications

  1. Sharkey LKR, Edwards TA, O Neill AJ (2016) ABC-F proteins mediate antibiotic resistance through ribosomal protection. mBio 7 DOI:10.1128/mBio.01975-15

  2. Tanner SJ, Ariza A, Richard CA, Kyle HF, Dods RL, Blondot ML, Wu W, Trincão J, Trinh CH, Hiscox JA, Carroll MW, Silman NJ, Eléouët JF, Edwards TA, Barr JN. (2014) Crystal structure of the essential transcription antiterminator M2-1 protein of human respiratory syncytial virus and implications of its phosphorylation. Proc Natl Acad Sci USA 111 1580–1585, doi: 10.1073/pnas.1317262111 

  3. Ariza A; Tanner SJ; Walter CT; Dent KC; Shepherd DA; Wu W; Matthews SV; Hiscox JA; Green TJ; Luo M; Elliott RM; Fooks AR; Ashcroft AE; Stonehouse NJ; Ranson NA; Barr JN; Edwards TA (2013) Nucleocapsid protein structures from orthobunyaviruses reveal insight into ribonucleoprotein architecture and RNA polymerization. Nucleic Acids Res 41(11):5912-26. doi: 10.1093/nar/gkt268

  4. Surtees R, Ariza A, Punch EK, Trinh CH, Dowall SD, Hewson R, Hiscox JA, Barr JN, Edwards TA (2015) The crystal structure of the Hazara virus nucleocapsid protein BMC Structural Biology DOI:10.1186/s12900-015-0051-3