Jenny Martin

Structural Biology and Structure-Based Drug Discovery

STRUCTURAL BIOLOGY: A seminal discovery was the first structure determination of an oxidative folding catalyst, the E coli DsbA enzyme (Nature, 1993). In solving this structure, Jenny became one of the first in the world to use selenomethionine labelling and MAD methods to determine a protein crystal structure. The structure revealed that DsbA has a thioredoxin fold and Jenny showed that this fold is extraordinarily tolerant to insertions/additions, giving rise to diverse functions. Her paper describing the thioredoxin fold (Structure, 1995) has become a classic in the field. Her team also uses cutting edge innovations that combine complementary techniques (X-ray, SAXS, SANS, mass spec, modelling, ITC, chemical cross-links etc) applied to membrane trafficking proteins to unravel the interactions of these highly dynamic systems (Traffic, 2006; PNAS 2007; PNAS 2011; PNAS 2012). STRUCTURE-BASED DRUG DISCOVERY: At Oxford, Jenny designed inhibitors of glycogen phosphorylase as potential antidiabetics (Biochemistry, 1989) (patents to Bristol-Myers Squibb, Janssen). As an ARC QEII Fellow, she solved the crystal structures of HIV-protease:inhibitor complexes in collaboration with Professor David Fairlie at UQ (JACS, 1995; JACS, 1996; Biochemistry 1999; J Med Chem 2000; J Med Chem 2004; 2 patents). Her QEII Fellowship also supported research on conotoxins - venom components of poisonous Cone snails that are important pharmacological tools with enormous therapeutic potential. The conotoxin crystal structures (Structure, 1996; Biochemistry 1996; 1997, 1998) were the first in the field and helped explain their exceptional stability and exquisite specificity. Jenny's ARC Australian Laureate Fellowship aims to develop inhibitors of DsbA and DsbB (a membrane protein) as potential new antibacterials to overcome antibiotic resistance.