The fourth-year PhD student in oral biology at the Dr. Gerald Niznick College of Dentistry is studying Pseudomonas aeruginosa, a multidrug-resistant bacterium that causes serious infections, like those in the lungs of people with cystic fibrosis.

Because antibiotics and other drugs don’t work against this bacterium, Haque is working on an alternative approach. He’s targeting the mechanisms the bacterium uses to cause disease.

Haque is focused on Pseudomonas aeruginosa’s type VI secretion system, which is a needle-like device that injects harmful proteins into cells. Haque said it isn’t well understood, so he’s investigating the function and regulation of the type VI secretion system to learn about bacterial interspecies and intercellular interactions. He hopes this research leads to the development of a drug in the near future that’s successful against Pseudomonas aeruginosa.

UM Today sat down with Haque to learn about what motivates him and his experience as a PhD student at UM. 

Why did you choose UM for your PhD?

After completing my bachelor’s and master’s at Jahangirnagar University in Dhaka, Bangladesh, I was seeking exciting opportunities in the field of microbiology. When I was looking for universities to do my PhD at, I came across Dr. Kangmin Duan, who is a professor of oral biology and cross appointed with medical microbiology and infectious diseases, so that caught my attention. I then read his research work and was eager to join his lab.   

What motivates you to do the work you do?

Many people with cystic fibrosis don’t get to celebrate their 40^th birthday. People are suffering. Antibiotics don’t work on Pseudomonas aeruginosa, and we have to do something about it. We must fight against these pathogenic microorganisms. Our research is coming at it with a different approach to help save lives.

What has been most rewarding during your time at UM?

I’ve received an International Graduate Student Scholarship, a University of Manitoba Graduate Fellowship and a Faculty of Graduate Studies Research Completion Scholarship. I have worked as a counselor with the University of Manitoba Graduate Students’ Association and am currently working as a graduate student representative at Dr. Gerald Niznick College of Dentistry, which is rewarding. And I’ve had the opportunity to present my research at two Canadian Society of Microbiologists annual meetings and I also presented at two Manitoba Dental Association (MDA) conferences.

At the MDA conferences, you won the prize the last two years for the best basic research poster as part of the Dr. Gerald Niznick College of Dentistry’s Research Day. What’s the secret to your success?

I have to thank my supervisor Dr. Kangmin Duan. I look up to him a lot. He’s my mentor and he motivates me to do better. He always provides feedback and tips to improve myself.  I would also like to thank my committee members Dr. Raj Bhullar, Dr. Prashen Chelikani and Dr. Silvia Cardona for their feedback during my studies. I’m also a hard-working guy, so I think that’s my secret. If you have passion to achieve something, you can do it.

What do you love about the work you do?

As microbiologists, we have the responsibility to win the battle against pathogenic microbes. The key to winning this war is to study the mechanism and function of these life-threatening microorganisms and discover how to stop them. It will be a truly rewarding experience for me when I can save lives through my research.

What are your plans once you finish your PhD?

I’m passionate about research and will contribute to the health sector. I want to stay in academia and become an independent researcher.

This Q&A is part of a series on UM Today this summer featuring Rady Faculty of Health Sciences graduate students. You will be able to find more grad student profiles here: #Radygradstudents.

The microbiologist researches how bacteria cause infectious diseases and become resistant to antimicrobial (antibiotic) drugs.

The increasing resistance of bacteria to antibiotics poses a global health threat, he says.

“Antibiotics used to be wonder drugs. But now, because of antimicrobial resistance, the treatments aren’t working in an increasing number of cases. We need to find new medicines.”

The Chinese-born Duan is a professor of oral biology in the Dr. Gerald Niznick College of Dentistry, with a cross-appointment in medical microbiology and infectious diseases in the Max Rady College of Medicine. He is also a researcher with the Children’s Hospital Research Institute of Manitoba and belongs to the Manitoba Chemosensory Biology Research Group.

Many of his studies in journals such as Molecular Microbiology have shed light on Pseudomonas aeruginosa, a multidrug-resistant bacterium that causes serious infections, such as those in the lungs of people with cystic fibrosis.

New antibacterial drugs that work in standard ways will inevitably fall victim to antimicrobial resistance, Duan says. So his lab is taking an alternative approach: targeting the mechanisms by which bacteria cause disease. The goal is to develop medicines that render bacteria harmless instead of killing them, because it’s the drive to survive that causes bacteria to become drug resistant.

“We aim to develop drugs that inhibit the virulence of disease-causing bacteria, rather than the viability,” Duan says. “To do that, we’re experimenting with ancient herbal medicines.”

Duan grew up seeing traditional Chinese medicines successfully used to treat symptoms that resemble those of infectious diseases, from skin problems to diarrhea.

Researchers have found bacteria-killing agents in these herbal remedies, he says, but so far none has been developed into an antibacterial drug because of low efficacy or high toxicity.

Traditional Chinese medicines seem to work, Duan says, and he wants to understand what mechanisms are at play. A study he co-authored last year, published in Antibiotics, looked at the effectiveness of a chemical compound found in Chinese herbs in reducing “virulence factors” of Pseudomonas aeruginosa. The compound significantly reduced mortality in mice infected with the bacterium.

“These results are encouraging,” he says. “This compound is a promising drug candidate.”

Duan started his scientific education at China’s Northwest University. He then moved to Australia to earn a master’s and PhD at the University of New South Wales.

He was a professor at Northwest University and an adjunct professor at the University of Calgary before joining UM in 2010.

He says he enjoys being part of the oral biology department at UM because of the collegial atmosphere and the researchers with eclectic interests.

Alongside his antimicrobial research, he is currently studying how bacteria interact with each other in microbial “communities,” and how they interact with human hosts.

He is also working on a project with oral biology colleagues to understand whether tooth resorption – the progressive loss of the inner tissue of teeth or the material covering teeth’s roots – is associated with microorganisms in the mouth.

Amanda Finch, a second-year dentistry student, was one of four winners of the research poster competition at the Dr. Gerald Niznick College of Dentistry’s annual Research Day, held in January at the RBC Convention Centre in conjunction with the Manitoba Dental Association’s 2019 convention.

Finch is among about 40 per cent of U of M dentistry students who choose to pursue a second degree – a bachelor of science in dentistry – while completing their professional degree. The science degree program provides students with a stipend to conduct research in the summers while they’re studying to become dentists during the academic year. 

Finch is part of a research team that has developed and is pilot-testing a questionnaire for parents to assess the risk of tooth decay in preschool children.

“It’s nice to have a different perspective on dentistry,” Finch said. “You see a whole different side of it through research. Next summer we’ll be looking at data that was collected with this tool.”

Dr. Raj Bhullar, associate dean (research) at the dental college in the Rady Faculty of Health Sciences, said the dental convention makes an ideal setting for Research Day. “It provides students with a very good opportunity to interact with practising dentists and showcase their work,” Bhullar said. “It’s also good for dentists to see what’s going on at the college.”

Participating in research, Bhullar added, helps students understand how to evaluate research findings – a skill they will need throughout their careers in order to stay current.

Dr. Kangmin Duan, associate professor of oral biology and a judge of the poster competition, said conducting research is relevant to the students’ future careers, no matter what path they take in dentistry. “It trains them in critical thinking. They’re learning the techniques to ask ‘why.’” 

The award for the top oral research presentation went to Manoj Medapati, a PhD student in oral biology, for a study of the role of bitter taste receptors in oral innate immunity. The oral presentations were judged by Dr. James Gilchrist, professor of oral biology.

Besides Finch, three students earned awards for their research posters after presenting them to four judges: Dr. Mitch Taillon, president of the Canadian Dental Association, Duan, and two other faculty members from the department of oral biology, Dr. Prashen Chelikani and Dr. Elliott Scott.

• Vivianne Cruz, a PhD student in oral biology, studied the role of the oral microbiota (micro-organisms in the mouth) in early childhood tooth decay.

• Israa Elgazzar, a fourth-year dentistry student, examined the causes and management of dental implant failure before the replacement tooth is attached to the implant.

• Stella Korowski, a fourth-year dentistry student, analyzed a survey of Manitoba dentists about their use of cone beam computed tomography (3D X-ray imaging).

The Manitoba Chemosensory Biology Research Group (MCSB) launched this past summer with a focus on the emerging field of chemosensation. A diverse group of researchers is exploring molecular, chemical and sensory biology towards the discovery of novel molecules that can alter or modify human chemical senses. The potential for the group is enormous in what is seen as a burgeoning area of research.

“It is an up and coming area,” said Dr. Prashen Chelikani, director, MCSB group and graduate chair in the College of Dentistry’s department of oral biology. “The work we are doing is multi-disciplinary and fairly well focused. When it comes to taste chemosensation, we are the only group in Canada right now.”

The four thrust areas of MCSB – taste, bacterial chemosensation, signal transduction and clinical applications of the science – cover virtually all areas of the human chemosensory experience. Potential applications from their research run the gamut from the food industry to clinical applications in myriad areas of health care.

“Clinical, pharmacology, consumer products, all those areas,” Chelikani said. “We’re looking at research on taste receptor biology, taste disorders, food chemistry, novel taste blockers and taste modifiers.”

Comprised of eight scientists from diverse disciplines across the University of Manitoba, the group targets research grants that fit with their areas of expertise. For the past several years now and in collaboration with Dr. Rotimi Aluko (dept. of human nutritional sciences), Chelikani’s lab has focused on developing taste modifiers. This area has already drawn immense interest from the food industry.

The group’s work however, goes well beyond consumer products. Microbiologists Drs. Ayush Kumar and Kangmin Duan are investigating how bacteria communicate with each other and with a host cell, a major factor in bacterial infections.

“We want to understand the mechanisms of antibiotic resistance and virulence in bacteria like Pseudomonas aeruginosa,” Kumar explained. “This organism is one of the most common pathogens causing lung infections in Cystic Fibrosis patients. Our role in the group is to understand how it may interact with the host defense mechanisms and if this interaction is linked to its antibiotic resistance.”

Collaborative research within MCSB is investigating the interactions between bacterial Acyl-Homoserine Lactones (AHL )signal molecules and human airway cells. The phenomenon that bitter taste receptors on lung epithelial cells serve as bacterial AHL receptors is being explored.

Dr. Robert Schroth, associate professor, Colleges of Dentistry, is interested in looking at the association between caries and taste in children and adolescents.

“This partnership will help to understand the role that taste may have in determining a child’s risk for developing caries (cavities), including early childhood caries,” he said.

To spur their research, members of the group review calls for research projects that dovetail into their respective areas of expertise. “When we apply for grants, we look at our own research and how we can mutually complement our expertise to strengthen the proposal,” Chelikani said, noting competition is often fierce for grant funding.

“The climate for peer–reviewed granting funding is very tough right now. You’re looking at 10 to 15 per cent success, depending on what you are applying for. In that scenario, collaboration is essential.”

Each member of the team has already enjoyed considerable success in their respective fields. The group is optimistic that banding together under the MCSB banner can better leverage future opportunities.

“We know we are focused and most of our principle investigators have good track records and significant, multi–year grants,” Chelikani said, adding it usually takes up to five years for a research group to determine how well it is performing. “The idea is for this group to become a Canadian Centre for Chemosensory Research down the road.”

The new multi-disciplinary Manitoba Chemosensory Biology Research Group builds on the College of Dentistry’s successful International Centre for Oral-Systemic Health (ICOSH), launched in 2008, and also envisioned as a nucleus for collaboration and innovation.

“ICOSH has received multiple international awards and recognition along with substantial government and private funding so we already know this model works.  Dr. Chelikani is uniquely qualified to lead this new group and I have no doubt that it will be extremely successful,” said Dr. Anthony M. Iacopino, Dean, College of Dentistry, Faculty of Health Sciences.