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McGowan Lab research

CollaborationsStudent research projects | Publications

About Associate Professor Sheena McGowan

Sheena McGowan was formally trained in microbiology (PhD Microbiology, 2004) where she developed a long-standing interest in structure and function of proteins. During her post-doctoral work she was trained in protein crystallography, biochemistry and biophysics. In 2011, she used the award of an ARC Future Fellowship to establish her own research group. Since that time, she has successfully initiated and driven various interdisciplinary collaborations that span both chemistry and molecular biosciences. Her research interests utilize a combination of structural biology, microbiology, medicinal chemistry and structure-based drug design that bridge fundamental microbiology and antibacterial drug discovery. Her multidisciplinary approach to research is mirrored in her teaching philosophy and she has also embraced the current movement away from traditional styles of course content delivery to a more innovative and active style of teaching and learning.


Our research

Current projects

1. Aminopeptidase inhibitors as a new drug class for infectious disease and cancer.
2. Anti-sporulation strategies for Clostridium difficile infections.
3. Structure-function studies of endolysin enzymes.
4. Toxic effectors delivered by the Acinetobacter Type VI secretion system.

Visit Associate Professor McGowan's Monash research profile to see a full listing of current projects.

Research activities

Structure, Function and Mechanism: the three pillars that drive discovery.

Bridging the gap between fundamental microbiology and drug discovery requires a complete understanding of how a new drug target works, both at an atomic level as well as its role in the microorganism. We focus on therapeutically important microbial proteins and aim to characterise how these proteins function on an atomic level. We investigate whether interruption of this function has therapeutic potential and then use our structural information to discover lead molecules and guide drug development. Current projects in the laboratory look at various proteins of interest from Plasmodium falciparum, Clostridium difficile, Acinetobacter spp, Staphylococcus aureus, Escherichia coli and other pathogenic Clostridium spp.

Current proteins under investigation include various aminopeptidases from parasites and bacteria as well as penicillin binding proteins from Clostridium difficile. All are attractive new targets for novel antimicrobials.

A new drug class: aminopeptidase inhibitors for malaria, cancer and infectious disease.

Protease enzymes represent 5-10% of all pharmaceutical targets being pursued for drug development. Aminopeptidases are a diverse set of protease enzymes and perform essential roles in all kingdoms of life. Their utility as drug targets for both infectious and chronic disease depends on our ability to modulate their activity. Our advanced structure-based drug design program has produced potential lead compounds for malaria and cancer as well as new routes to anti-virulence agents for bacteria. Our advanced structure-based drug design program has produced potential lead compounds for malaria and cancer as well as new routes to anti-virulence agents for bacteria.

Structure-based drug design has produced compounds that kill Plasmodium falciparum and Plasmodium vivax, two causative agents of human malaria. (Nyssa Drinkwater, Tess Malcolm, Jisook Lee). 

Harnessing the antibacterial power of phage: characterisation and engineering of phage endolysins.

The growing problem of antibiotic resistance underlies the critical need to develop new treatments to prevent and control resistant bacterial infection. Bacteriophage-encoded endolysin enzymes or lysins act to lyse their host bacterial cell wall at the end of the bacteriophage lytic reproductive cycle. Lysins are also attractive biotechnologies for primary industry; to prevent food contamination by foodborne pathogens or food spoilage bacteria and as diagnostic tools for rapid detection of bacteria from food, medical and environmental samples. Our team aims to understand the molecular details of how endolysins engage their bacterial host.

Lysin enzymes act to degrade the bacterial cell wall during the lytic cycle of a bacteriophage (A) or when applied to the outside of susceptible bacteria (B). Electron micrograph of cell wall digestion and lysis (C) courtesy of Daniel Nelson. (Sebastian Broendum, Blake Riley) 

Techniques/expertise

Structural biology (X-ray crystallography, cryo-electron microscopy, SAXS)
Computational biology (molecular dynamics, molecular docking, normal mode analysis)
Microbiology and biochemistry (in vitro susceptibility testing, kinetics, binding)
Biophysics (FRET, hydrogen-deuterium exchange mass spectroscopy)
Structure-activity based drug design

Disease models

(In collaboration) Prevention and treatment mouse models for bacterial and parasitic infections.


Collaborations

We collaborate with many scientists and research organisations around the world, allowing us to answer fundamental questions of biology with structure-function research, as well as develop a complete drug discovery platform primarily for the development of aminopeptidase inhibitors as potential therapeutics. Some of our more significant national and international collaborators are listed below. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).

Collaboration map_shadow

Chemistry 
Prof Marcin Drag (Wroclaw University, Poland & UCSD, USA)
Prof Rich Payne (University of Sydney)
Prof Peter Scammells (MIPS)
Profs Stephen Pyne & Paul Keller (University of Wollongong)

Parasitology
Prof Tania de Koning-Ward (Deakin University)
Prof Sergei Whittlin (SwissTPH)
A/Prof Darren Creek (MIPS)

Bacteriology
Prof Dena Lyras, (Monash)
A/Prof John Boyce, (Monash)
Prof Julian Rood, (Monash)
Cryo-em  Dr Matt Belousoff, (Monash)

Protein engineering 
A/Prof Ashley Buckle, (Monash)
Prof Colin Jackson (ANU)

Computational biology
Dr Wei Yang & A/Prof Cheng Guijuan (Chinese University of Hong Kong, Shenzhen)
Dr Haibo Yu (University of Wollongong)
Dr Ben Porebski (MRC, Cambridge)

Clinical pharmacology
Prof Susan Charman, (Monash)

Biophysics 
A/Prof Ganesh Anand, (National University of Singapore)
Dr Toby Bell, (Monash)

HTS drug discovery
Prof Vicky Avery, (Griffith University)


Student research projects

The McGowan Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.

Please visit Supervisor Connect to explore the projects currently available in the McGowan Lab.