Dr Su-Ling Loo

Dr Su-Ling Loo | Respiratory Researcher | HMRI

Research Interests

I am very interested in respiratory viruses, and how they impact those in the community who are particularly susceptible to infection, particularly those with respiratory diseases or the elderly. I have worked extensively with rhinoviruses and coronaviruses, and these are my main viruses of interest. They are both responsible for a vast majority of common colds.

I enjoy cellular biology, particularly epithelial cells that line the lungs. We can study a model of the lung epithelium using air-liquid interface cell culture. This allows the study of cells from healthy donors as well as those who have asthma or chronic obstructive pulmonary disease (COPD). These cells are grown exposed to air and they differentiate, produce mucus and even have beating cilia!

Tying all of these parts together, I examine the first response of the lung epithelium to virus infection or the innate immune response. This is triggered as soon as an epithelial cell detects the presence of virus, and unleashes cascading signals which lead to the release of interferons that “interfere” with virus replication and signal to warn other surrounding cells. We know that this first response can be dysregulated in epithelium from donors with respiratory disease.

During my PhD, I pioneered an in vitro model of coronavirus infection in differentiated primary human bronchial epithelial cells. I showed for the first time that two common cold coronaviruses, 229E and OC43, had very different replication kinetics in this model, as well as distinct induction of the innate anti-viral response. 229E had robust replication within 24 hours of infection and also induced a strong interferon response from the epithelial cells. In contrast, OC43 reached peak replication at 96 days post-infection and this infection did not resolve. Interestingly OC43 did not induce an interferon response from the cells and this may suggest why its replication went unhindered.

Through this study, I was able to show that non-pathogenic common cold coronaviruses are valuable to study particularly in light of emerging pathogenic coronaviruses such as SARS-CoV-2. OC43, in particular, shows similarities to pathogenic coronaviruses such as SARS-CoV-2 which can replicate without inducing an immune response, leading to asymptomatic transmission. This makes OC43 a useful virus to study treatments that aim to restore an anti-viral response to SARS-CoV-2. In addition, the study of pathogenic coronaviruses is particularly limited due to the dangers of working with them and the costs involved in setting up a PC3 lab with appropriate safety measures. The establishment of this coronavirus model with endemic coronaviruses may be a more accessible way for us to study SARS-CoV-2 characteristics, particularly since we can study epithelial cells from people with respiratory diseases and understand any mechanisms behind their reduced capability to fight infection.

After completion of my PhD, I joined the Viral Immunology and Respiratory disease group headed by Associate Professor Nathan Bartlett. I have been able to bring my technical expertise to many virus-related projects, working closely with several companies including Ena Therapeutics (MRCF-funded company) who has developed an innate immune stimulant that protects the lungs against respiratory virus infections. The foundational work I began in my PhD has led to several coronavirus projects since the emergence of COVID-19.

Why did you get into research?

Growing up with a family member who had severe allergies, and suffering from asthma myself as a child, I have always been interested in our immune system and the delicate balance that it must maintain between protecting us and harming us. In high school biology, viruses fascinated me. Finally, after completing my third-year project for Biomedical Sciences in a hospital, I knew that I wanted to work with human cells and in a clinical setting. I chose to do my honours combining all of these passions and went on to complete my PhD in this same field. My PhD was focused on the innate epithelial immune response to common cold coronaviruses, and showed that even various strains of coronavirus can be distinctly different from each other during infection.

What would be the ultimate goal for your research?

Respiratory viruses will always be part of our lives, from the common cold which means you have to stay home from work, to pandemics such as COVID19. The ultimate goal for my research would be to develop ways to combat respiratory viruses which are host-orientated rather than virus-orientated. This makes sense since viruses are incredibly diverse and new variants are emerging all the time. It would be amazing if we could boost the host immune response and equip the innate immune system to respond faster and more effectively once it detects a virus.

Biography

Dr Loo is a postdoctoral researcher who completed her PhD in 2018 and has since worked in Viral Immunology and Respiratory Disease group under Associate Professor Nathan Bartlett. During her PhD, she developed a coronavirus model of infection in air-liquid interface cultures, and has since applied her technical expertise to many projects involving other viruses and the culture of other epithelial cells such as primary corneal epithelial cells. With the emergence of COVID-19, Dr Loo was further involved in various projects for local businesses who wanted to test their products against coronavirus, for example, disinfectants, sanitizers and virus inactivating materials. Working closely with Ena Therapeutics, Dr Loo has been involved in screening their innate immune stimulant compounds in air-liquid interface cultures from donors with respiratory disease and the elderly.

Future Focus

My PhD serendipitously guided my interest in coronaviruses when no one was really interested in them: they weren’t the main heavyweight in causing the common cold (that goes to rhinovirus) and SARS and MERS were pandemics from long ago or far off places. COVID really challenged these perspectives.
My future focus is on furthering our understanding of both non-pathogenic and pathogenic coronaviruses as they will continue to be a part of our lives, and hand in hand with that is developing host-targeted anti-viral therapies for people with respiratory diseases. Boosting the innate immune system will not only provide a way to bridge the gap between the emergence of a pathogenic virus and the development of a vaccine, but will improve the lives of people who may experience life-threatening exacerbations from a common cold.

Specialised/Technical Skills

  • Human airway epithelial models
  • Virus growth, purification and titration
  • Primary cell culture
  • In vitro drug testing
  • Air-liquid interface cell-culture and monolayer cell culture
  • Cell biology
  • Real-time PCR, Standard PCR, Western Blotting, ELISA
  • Viral infections
  • Measuring cilia beat frequency

Affiliations

  • Priority Research Centre for Healthy Lungs
  • AUSREC
  • HMRI
     

Published Work