“Establishing and growing human organoids in culture dishes is revolutionising biomedical research, opening numerous possibilities, including but not limited to, studying human development, modelling human biology/pathology, testing therapeutic agents, and regeneration medicine.”
As the COVID-19 pandemic spread across the globe, many scientists began researching the causes, origins, and the pathogenesis of SARS-CoV-2. Most believe that bats have played a role in the zoonotic transmission chain of SARS-CoV-2 to humans.
However, at the early stages of the pandemic, researchers were having difficulty isolating SARS-CoV-2 from patients’ specimen, and other bat viruses.
To solve this, Dr. Jane Zhou Jie, Assistant Professor in the Department of Microbiology at HKUMed, experimented with bat intestinal organoids and tested SARS-CoV-2’s ability to infect these lab-grown bat cells.
Her hunch was confirmed, and her findings were published in Nature Medicine. Findings from her study are now being used to assist researchers in studying SARS-CoV-2 and other bat viruses.
We spoke with Dr. Zhou about her study “Infection of bat and human intestinal organoids by SARS-CoV-2”, and why she believes organoids are important for future studies of infectious diseases.
Thank you for joining us, Dr. Zhou.
Thank you for having me.
When did you start working with organoids?
Around five years ago. Organoids came into my view. I jumped onto them immediately.
Why did you jump onto using organoids right away?
As biomedical scientists, we are studying the human biology of pathology. However, apart from fibroblasts, there are few cells in the human body that can be maintained long-term and stably and expanded in vitro.
Thanks to my pathology training, it was very clear to me that it is impossible for conventional cell lines to model the native cells in the human body.
Being aware of this did not help at all since there are no readily accessible in vitro models that can replace cell lines for routine research purposes.
What is the strength of organoid cultures over other in vitro systems?
The beauty of organoid culture is that it enables the long-term expansion of native epithelial cells in vitro.
As such, many biological processes in live tissues can be studied in culture dishes and plates.
This was a major breakthrough in human biology.
Compared to using animals to study infectious diseases, what is the benefit of using organoids?
Experimental animals such as mice are extensively utilized to study infectious diseases.
However, animal models have limitations, including the intrinsic biological difference between mouse and human, among others.
As a result, animal experiments frequently fail to recapitulate the pathophysiology of human infections.
How do you see the future of biomedical research being impacted by organoids?
Establishing and growing human organoids in culture dishes is revolutionising biomedical research, opening numerous possibilities, including but not limited to, studying human development, modelling human biology/pathology, testing therapeutic agents, and regeneration medicine.
For research on respiratory viruses, how do these organoid systems help?
Respiratory organoids may represent the optimal model systems to study respiratory viruses.
However, our current organoids only contain epithelial component. Our hope is to further develop our organoids for better simulation of the human respiratory tissue.
Another exciting area for organoids we hear about often are human airway organoids, why is that?
Human airway organoids can mimic the native airway epithelium.
In our earlier publication in PNAS, we demonstrated that these airway organoids can be utilised to assess the infectivity of emerging influenza viruses in humans.
Now, we are using these airway organoids to study the respiratory infection of SARS-CoV-2 .
You recently used bat intestinal organoids to research SARS-CoV-2, can you tell me more about this?
I have never touched bat viruses previously. In the advent of SARS-CoV-2, I came to realise that most bat viruses were unable to be isolated, which hampered the understanding of bat viruses, Especially the zoonotic potential of these viruses.
Plenty of previous surveillance studies, including ours, indicated that SARS related coronaviruses can infect bat intestinal cells. Then I was thinking, if I can establish organoid culture for bat intestine, I could resolve the problem of bat virus isolation.
In addition, when the initial infection cases emerged in Hong Kong this January, our colleagues were struggling to isolate SARS-CoV-2. SARS-CoV-2 is very similar to many SARS related coronaviruses found in bats. I speculated that maybe bat organoids can help the isolation. Indeed, SARS-CoV-2 grew very well in bat intestinal organoids.
After we published in Nature Medicine, several virologists studying bat viruses approached us for collaboration. These bat organoids provided a brand-new and unique model system to isolate and study numerous bat viruses.
In relation to the pathogenic pathways for Sars-Cov-2, what questions do you believe still need to be answered about COVID-19?
I want to figure out why COVID-19 is highly transmissible. What is the cellular basis in the human respiratory epithelium, the primary infection site for SARS-CoV-2 infections?
You first started as a doctor, what made you become interested in research?
When I started doing research, I found my true self, a passionate and confident self.
I firmly believe science is the driving force of the world. I feel very proud to be a scientist.
For other doctors and researchers, who may be interested in organoid research, any advice you would give them?
Organoid technology is now changing the landscape of human biology. Embrace it.
Enjoy the power and beauty of organoids.