Clement Tsui: searching for new approaches to treat tuberculosis

4 May 2018

Tuberculosis is one of the top ten causes of death worldwide. 1.7 million people died from the disease in 2016, and 10.4 million people were exposed. The bacteria that causes tuberculosis, Mycobacterium tuberculosis, is typically airborne, spread via coughing, and the inhalation of contaminated air droplets.

Dr Clement Tsui (Croucher Fellowship 2002) began to study tuberculosis in 2016, when he joined the laboratory of Dr Yossef Av-Gay, in the Faculty of Medicine in the University of British Columbia. The awareness of the global importance of tuberculosis, paired with an interest in tackling multi-drug resistance, focused Tsui’s study on the discovery of novel drug candidates with different modes of action, taking a combined chemical genetics approach. Unlike bacterial pathogens such as E. coli or Cholera, multi-drug resistant tuberculosis has intracellular lifestyle and infects our body’s macrophages (a white blood cell type that normally destroys the bacteria). The bacteria multiply inside these macrophages, which then attack the body when released or burst.

The laboratory of Dr Av-Gay has developed a method of discovering novel compounds that could be used to treat tuberculosis via the use of a parental strain or wild type tuberculosis within macrophages, after their exposure to various chemical compounds. Some of these compounds are toxic and are known to inhibit tuberculosis growth. If the wild type strain survives against these compounds, in theory, it will have developed resistance to the selected compounds through mutation in the potential drug target. By comparing the genome of the wild type to resistant mutant strains at the molecular level, Tsui and his teammates aim to characterise the potential drug targets, using the next-generation sequencing technologies, and bioinformatics analysis of the genomic data.

Mutations in the genome may lead to changes in gene expression or to the protein structure of tuberculosis, and any mutations can be examined to explore whether they are related to the pathogen’s growth and survival in macrophages.

Dr Clement Tsui, Croucher Fellowship 2002

At the University of British Columbia, Tsui used an intracellular drug screening approach, giving the team a more accurate look at the environment in which the bacteria lives, replicates, and spreads. The end goal remains novel drug discovery to realise the eradication of tuberculosis.

In February 2018, Tsui accepted a new position at Sidra Medicine, a hospital and medical research center located in Qatar. In his new position, he is using whole genome sequencing and metagenomic approaches to characterise infectious diseases, including viruses, bacteria, parasites and fungi. The work explores epidemic and outbreak dynamics, aiming to discover how pathogens are transmitted from patient to patient.

His exploration of bacterial drug-resistance mechanisms has continued in this role. Making use of next-generation sequencing technologies, Tsui is attempting to understand the mechanisms of this resistance at the genomic level. The data produced will be vital to the hospital’s infection control, assisting with monitoring the spread of pathogens, reducing the amount of time spent in disease diagnostics, and additionally uncovering information which could also be translated into a higher standard of patient care.

“As a scientist, you want to discover new knowledge, but at the same time you want to contribute the knowledge to the community or to the society, and at the moment I feel that medical microbiology is helping people to understand more about infectious diseases, and this is something that keeps me invested and motivated,” said Tsui.

In 1996, Dr Clement Tsui graduated from the University of Hong Kong (HKU) with a BSc in Environmental Science. His subsequent PhD research focused in part on the effects of pollution on freshwater fungi (HKU, 2000), and since then he has researched the evolution and genomics of pathogens in plants, animals and humans across Hong Kong, Canada, and Australia. He is currently working as a Molecular Scientist within the Department of Pathology at Sidra Medical and Research Centre in Qatar.

To view Dr Tsui’s Croucher profile, please click here.