Cell crosstalk: Five years, five papers, new knowledge
Astra Zeneca researcher Jie Ji spent five years at Karolinska Institutet (KI) on advanced lung airway research using Inhalation Sciences’ technology. The project will produce a total of five papers and forward understanding of how airway cells interact with each other to trigger inflammation and immunity. Why is understanding cell-to-cell interaction in our airways so vital?
“Every time we breathe in a toxic particle or pathogen the cells lining our airways are our first line of defence. And they don’t just act against pollutants—they collaborate with each other. Releasing pro-inflammatory cytokines, and orchestrating our body’s immune response. Understanding how the crosstalk between cells helps manage inflammation and create immunity was central to my PhD research.”
The result was Jie Ji’s 100-page thesis “The development of multi-cellular human lung models to study inflammatory mechanisms and cell-cell interactions”. Her doctoral work has already generated two papers and there are three more to come. A substantial body of work from a young scientist with ten publications already to her name and who has recently finished her first month as research scientist at Astra Zeneca.
“In total my work using XposeALI will generate five papers,” she says. “Two already published. Two being completed. And one in progress.
Why is understanding cell-to-cell interaction in the airways so important?
“Immune effector cells, like macrophages, neutrophils and dendritic cells – and structural cells, like epithelial cells and fibroblasts, are our first line of defence. Investigating the mechanisms behind the toxic effects of inhaled particles is crucial. Then, instead of just knowing ‘this is toxic’, you can take effective action to avoid it. You know better how to cure yourself if you get an infection, and how inhaled particles influence our immune system and host of defence. Also, we’re seeing cellular treatment becoming more and more popular. For example, CAR-T therapy. The T cells are extracted from patients and then genetically modified to express a CAR in vitro condition, and finally reinfused into the patients to fight, say, cancer cells. So cell-to-cell interaction may be able to give us some hint of a future cell treatment.”
Throughout your research at KI you’ve used Inhalation Sciences equipment: The PreciseInhale aerosol generator platform. And XposeALI, its cell culturing module that cultures in vitro lung cells using an Air Liquid Interface. How much did the systems evolve and develop over the four years?
“A lot! In fact they kept continuously developing. Just a couple of examples: Before, we didn’t have a humidity feature. So we used a tray full of medium underneath the inserts to keep the cells alive. But now we have a customized plastic plate with three separate wells that can separate the different inserts and avoid contamination. And before we used softer tubes which were not that user-friendly. So the ISAB team changed them to metal tubes, which are a lot more time-efficient in the lab. Now it takes just one second to put them together.”
With a BSc in Biotechnology from Soochow University in China and your MSc in Toxicology from KI, as well as your PhD, do you think inhalation science is in a good state at the moment?
“Absolutely! Yes! I mean the WHO tell us that currently 1-in-9 deaths are caused by air pollution. I think we’re all realizing how urgent it is to investigate. It’s certainly something I thought about when I decided to go int
o toxicology. I felt very strongly that this is something science really should respond to. And I think recently with the growth in our understanding of PM 2.5, particles less than 2.5 micrometres in diameter, and how they can penetrate deep into the lung, we are seeing a big acceleration in our understanding of how every part of inhalation, particle behaviour and cell-to-cell behaviour impacts us.”
You’ve been at Astra Zeneca for one month now. How are you finding it?
“It’s my dream company and my dream job! They’re doing such a lot of interesting stuff. I really want to explore a different environment and a more industrial setting after being in academia for a long time. And it’s great I’m learning a lot!”