Natalie Zeytuni, of the Strynadka Lab in the Department of Molecular Biology and Biochemistry, is a recipient of a 2015-2016 Banting Postdoctoral Fellowship. Antibiotic resistant TB is a growing global health threat. Zeytuni’s research focuses on understanding the molecular structures that the TB bacterium uses to invade and infect cells in our bodies, with the goal of finding ways to stop its spread.
Research topic
Research Description
Mycobacterium tuberculosis (TB), once considered a disease of the past, is making a significant comeback. Until the early 1990s, first-line anti-TB drugs were highly effective. TB has since reemerged in the past decade by acquiring multiple mechanisms of drug resistance and, once again, threatening world healthcare.
The latest numbers in Canada show an increase in infections of four percent per year, with Aboriginal populations having seen no drop in infection in 30 years and over twice as much at risk.
TB is killing more than two million people every year with estimates of nine million each year. The new multidrug resistant strains of TB are now surviving first-line antibiotics, requiring patients to undergo a second round of antibiotics. These second-line antibiotics are much tougher on the patient and are leading to further antibiotic resistance.
Several countries are now reporting extensively drug-resistant TB strains that are effectively untreatable. Due to the highly infectious nature of TB, these new drug-resistant strains could easily become the next global pandemic. For this reasons, better understanding of TB operation is needed to further anti-TB efforts.
One such anti-TB target is the type VII secretion system (T7SS), this system is used by Mycobacteria, such as TB, to transport invasion tools across TB’s outer membrane that are necessary to invade and infect a target cell.
My research aims to elucidate the molecular structure of T7SS – by understanding the three-dimensional structure of the complex, it can be understood how it interacts with specific targets, and crucially how to inhibit it.
Why did you decide to pursue a postdoctoral fellowship at UBC? Did you consider other opportunities?
The laboratory of Prof. Natalie Strynadka at UBC is internationally renowned in microbial research and structural biology—especially in technically demanding fields of membrane associated proteins and multi-protein complexes. Prof. Strynadka is famed as an excellent researcher, being personally recognised by both the Royal Society (London) and the Royal Society of Canada, whilst her work has received international funding from the likes of the NIH, Wellcome Trust and the HHMI.
UBC is ideally situated as a host institute. Thanks to a Canadian Foundation for Innovation fund, UBC hosts the Advanced Structural Research in Infectious Disease (ASTRID) initiative. This fund provides state-of-the-art infrastructure in structural biology and the Centre for TB Research investigating all aspects of TB research from the molecular level, in the Centre for Disease Modelling, to the clinical in the Centre for Drug Research and Discovery. It is my belief that UBC and the Strynadka laboratory is the only place in Canada, and one of the few worldwide, that could provide such broad spectrum training and close scientific collaborations.
What do you hope to accomplish with your current work?
My time in the Strynadka laboratory focuses upon the structural, biochemical and inhibitory analysis of the Type VII Secretion System, essential for Mycobacterial tuberculosis (TB) pathogenesis. While the Strynadka laboratory and UBC infrastructural will allow me to extend my skill-set in the technical fields of cell-free membrane protein expression, EM and stable isotope labelling by amino acids in cell culture mass spectrometry (SILAC-MS). These complementary techniques are novel and constantly being developed, adding valuable contributions otherwise impossible. Their inclusion to any work is highly original and impactful – especially when applied to membrane spanning proteins.