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Senior Research Fellow - Sir Charles Hercus Health Research Fellow

Email matthew.mcneil@otago.ac.nz
Tel +64 3 479 8373

PhD (University of Otago), BSc(Hons) First Class (University of Otago

Year of appointment: 2018

Previous academic positions

2015-2018: Postdoctoral Scientist, Infectious Disease Research Institute, Seattle, USA.

2013-2015: Postdoctoral Scientist, Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.

2012-2013: Postdoctoral Scientist, Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.

Current research

The overarching goal of this research programme is focused on the development of novel treatment strategies to combat Mycobacterium tuberculosis, the causative agent of Tuberculosis and a significant cause of infectious disease morbidity and mortality.

Current research themes include:

  1. Understanding and exploiting the biological costs of drug-resistance.
  2. Understanding the interactions between antibiotic targets to design novel combination therapies.
  3. Identifying strategies to enhance antibiotic lethality.
  4. Validation of novel drug targets in M. tuberculosis to guide antibiotic development.

This research utilizes a combination of molecular biology, microbiology, antimicrobial susceptibility testing, biochemical assays, next generation sequencing and metabolomics. This work involves the use auxotrophic-avirulent PC2 approved strains of M. tuberculosis, virulent strains of M. tuberculosis that require PC3 containment and the fast-growing model species Mycobacterium smegmatis.

Research team

Scientific Staff

  • Dr Will Jowsey
  • Dr XinYue Wang
  • Dr Cara Adolph
  • James Cheung
  • Hannah Klaus

Current post graduate students (Co-Supervised)

PhD: Natalie Waller, Cassie Chapman

BSc(Hons): Michael Chrisp

Former post graduate students (Co-Supervised)

BSc(Hons): Imogen Samuels, Cassie Chapman, Noon Seeto, Laura Keighley, Natalie Waller, Heath Ryburn

MSc: Heath Ryburn

PhD: Cara Adolph

Funding

University of Otago Research Grant (2024)
Defining bioenergetic dysregulation in an ATP synthase bedaquiline resistant mutant of Mycobacterium tuberculosis
$45,028 (Principal Investigator)

HRC-NZ Project Grant (2022-2025)
Targeting metabolic dysregulation to eradicate drug resistant M. tuberculosis
$1,199,544 (Principal Investigator)

Sir Charles Hercus Fellowship (HRC-NZ) (2022-2026)
Dysregulating metabolism to eradicate drug-resistant Mycobacterium tuberculosis
$582,826 (Principal Investigator)

Marsden-Project (Royal Society of New Zealand) (2021-2024)
How does allostery modulate bacterial pathogenesis?
$939,000 (Associate Investigator)

China-Maurice Wilkins Centre Collaborative Research Programme (2021-2023)
Exploiting synergistic interaction in energy metabolism to combat drug resistant pathogens
$527,253 (Co-Principal Investigator)

HRC-NSFC Biomedical Collaboration Fund-Project (2020-2023)
Targeting succinate metabolism to produce new chemotherapeutic agents
$699,695 (Associate Investigator)

HRC-NZ Project Grant (2020-2023)
Combatting antimicrobial resistance with high throughput bacterial genetics
$1,199,272 (Principal Investigator)

Maurice Wilkins Centre Flexible Research Grant: Category 2 (2019-2021)
Exploring synthetically lethal interaction in mycobacterial bioenergetics
$9000 (Principal Investigator)

Maurice Wilkins Centre Flexible Research Grant: Category 2. (2019-2021)
Genetic characterisation of drug resistant M. tuberculosis to guide the therapeutic exploitation of collateral susceptibilities
$24000 (Principal Investigator)

Marsden Fast Start (Royal Society of New Zealand) (2018-2021)
Exploiting the costs of drug resistance to design new therapeutic regimens against M. tuberculosis
$300,000 (Principal Investigator)

HRC-NZ Programme Grant (2018-2020)
Targeting pathogen energetics to produce new antimicrobials.
Partial funding for years 1-2, $1,000,000 (Associate Investigator)

With MSc student Natalie Waller

Publications

Adolph, C., Cheung, C.-Y., McNeil, M. B., Jowsey, W. J., Williams, Z. C., Hards, K., Harold, L. K., … Tyndall, J. D. A., … Cook, G. M. (2024). A dual-targeting succinate dehydrogenase and F1Fo-ATP synthase inhibitor rapidly sterilizes replicating and non-replicating Mycobacterium tuberculosis. Cell Chemical Biology, 31(4), 683-698. doi: 10.1016/j.chembiol.2023.12.002 Journal - Research Article

Jowsey, W. J., Cook, G. M., & McNeil, M. B. (2024). Antibiotic resistance in Mycobacterium tuberculosis alters tolerance to cell wall-targeting inhibitors. JAC: Antimicrobial Resistance, 6(3), dlae086. doi: 10.1093/jacamr/dlae086 Journal - Research Article

Cook, G. M., & McNeil, M. B. (2024). Enzyme blueprints will aid tuberculosis drug design. Nature, 631, 278-280. doi: 10.1038/d41586-024-02094-1 Journal - Research Other

Wang, X., Jowsey, W. J., Cheung, C.-Y., Smart, C. J., Klaus, H. R., Seeto, N. E. J., Waller, N. J. E., … Fineran, P. C., Cook, G. M., Jackson, S. A., & McNeil, M. B. (2024). Whole genome CRISPRi screening identifies druggable vulnerabilities in an isoniazid resistant strain of Mycobacterium tuberculosis. Nature Communications, 15, 9791. doi: 10.1038/s41467-024-54072-w Journal - Research Article

Waller, N. J. E., Cheung, C.-Y., Cook, G. M., & McNeil, M. B. (2023). The evolution of antibiotic resistance is associated with collateral drug phenotypes in Mycobacterium tuberculosis. Nature Communications, 14, 1517. doi: 10.1038/s41467-023-37184-7 Journal - Research Article

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