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Professor Leo Brady

Structural biology of pathogenesis

As a structural biologist, I am interested in understanding biological systems at a molecular level. This is achieved by primarily using the technique of protein crystallography. A principal focus of our studies is the study and exploitation of proteins central to human disease. Our work is interdisciplinary, encompasses both basic and applied studies, and we work in close collaboration with a wide range of academic and industrial groups. 

Career research highlights include:

  • The first structure of a lipase [Nature (1989) 343, 767-770], and two fungal amylases [Biochemistry 29, 6244-6249]. These structures have since contributed to protein engineering studies resulting in improved recombinant products with both medical and commercial applications.
  • HIV Proteins:  Studies of the HIV receptor, CD4 [Science (1989) 260, 979-983], and the integrase enzyme from the virus [TIBTech, 15, 167-172], a challenging drug target on which we worked closely with both Glaxo and Proteus, a small UK-based biotechnology company. From these studies a strong interest in structure-based drug design techniques emerged.
  • Immune System proteins: We worked with Celltech to determine a number of engineered antibody structures [J. Mol. Biol. (1992) 227, 253-264; Proteins SF&G (1997) 29, 161-171] which contributed to the development of products now commercialised by Celltech as diagnostic and therapeutic reagents for the treatment of colonic and breast cancers. Our fortuitous discovery that recombinant forms of the CD2 receptor could adopt more than one protein fold [PNAS (1995) 92, 7337-7341] provided us with a unique opportunity to probe the folding pathway and evolution of immunoglobulin domains [Nature Struct. Biol. (1998) 5, 778-782; J. Mol. Biol.(1999) 285, 1857-1867].
  • Anti-malarials and Dehydrogenases:  With GSK we developed potential drugs against the lactate dehydrogenase from Plasmodium falciparum - the causative agent of malaria [Nature Struct. Biol.(1996) 3, 912-915; J. Biol. Chem. (1999) 274, 10213-1021, J. Biol. Chem. (2004)  279, 30, 31429-31439] and have also studied the PfATPase6 transporter, one of the targets of artemisinins [Nature Struct. & Molec. Biology (2005) 12, 628 – 629].
  • Other interests include neuroscience targets (neurotrophin-TrkB complex, Structure (2001) 9, 1191-1199); the RKIP/PEBP family of signalling proteins and their relationship to cell growth and oncology [Structure (1998) 6, 1245-1254, EMBO J (2006) 25, 605-614], bacterial adh esins and novel vaccines [EMBO J. (2008) 27, 1779-89; PNAS  (2011) 108, 15174-15178]; and most recently an expanding programme of designer proteins for synthetic biology  [Nature Chem Biol  (2011] 7, 935-941; PNAS.(2012) 109(33)13266-71, J. Am. Chem Soc.(2013)135(34),12524-12527].

Research keywords

  • Structural biology
  • protein crystallography
  • drug design
  • cell surface receptors
  • bacterial adhesins
  • designer proteins
  • malaria
  • trypanosomes

Researchers