Fly eyes: modelling cell growth and adhesion patterns
Developmental biology aims to decipher the fundamental principles that govern cells' organisation within tissues. Tissues are complex arrangements of cells, which adhere, grow, and differentiate with intimate communication between them. When a seminal study highlighted intriguing similarities between tension surface in clusters of soap bubbles and cell organisation within tissues, it quickly became apparent that it is possible to model and predict cell behaviour during tissue development using mathematical models.
Growth patterns
Chan focuses on fruit fly eye formation as it involves complex cell shaping and cell-to-cell contact, all essential for the development of a functional organ. E- and N-cadherin are essential components in retina development.
These transmembrane proteins are essential for adhesion (how a cell binds to neighbouring cells) and they also attach to intracellular cytoskeleton and signalling components (contributing to cell shape). The interaction of E- and N-cadherin with the contractile intracellular protein actomyosin is a driving force in eye cell pattern formation.
How do E- and N-cadherin together with actomyosin control cell shape? How do these molecules interact with each other and could we access their contribution to cell shape quantitatively?
To unveil the molecular mechanisms driving eye formation, Chan manipulates the expression of Cadherins and actomyosin using the sophisticated genetic techniques available for studying fruit flies.
How these modulations affect eye formation can then be monitored using live imaging microscopy. These observations are further integrated into a mathematical model for quantitative analysis and prediction of cell shape under various circumstances.
Chan’s doctoral study focused on the molecular mechanisms of cell division in human cells and led her to investigate the connection between growth control and the Hippo signalling pathway.
From cell division to tissue development, Chan switched to fruit flies, a model organism, explaining, “I wanted to learn and really understand biology through the up close and personal method of microscopy and imaging.”
Fruit flies have long been popular subjects for genetic research, but their cellular makeup also makes them ideal for Chan’s work.
“Cell patterns in fly eyes are very beautiful, and this mathematical aesthetic is continued on a cellular level, as the geometry of the cells follows physics principles,” she says.
About 70 percent of disease-related genes in humans are also found in fruit flies, making them an extremely relevant model for research. Furthermore, fruit fly genomes have also been extensively sequenced, allowing amenable genetic manipulation. Fruit flies are also very fast growing, allowing the monitoring of offspring over many generations in a relatively short amount of time. Hence, fruit flies stand as an ideal organism to study. “Fruit flies were perfect models, especially given my attraction to all those beautiful epithelial images!”
Interdisciplinary research
Chan further stresses the importance of investigating fundamental biological processes in model organisms, and more specifically in advancing fundamental understanding of E- and N-cadherin functions. Indeed, these factors have a strong yet unclear implication in a process called EMT (Epithelial To Mesenchymal transition), at the basis of solid tumour evolution into metastatic cells during cancer progression. Therefore, understanding their dynamics could shed light on cancer etiology.
“As a molecular/cell/developmental biologist, I am a minority on the team, since most of the others are physicists or biophysicists and we all work on different organisms and projects. In the beginning, I felt like we were in the Tower of Babel, because we all speak different scientific languages,” Chan says.
The new atmosphere encouraged collaboration, making the adjustment easier. As a strong experimental biologist, Chan has a good hand for performing experiments to test hypotheses. This is complemented by the lab’s physicists and theorists who have very strong analytical skills, which strengthens Chan’s work with different and innovative ideas.
The unique nature of the lab makes it an incredibly stimulating environment for scientific creativity for biologists and others to answer their burning questions.
“Working in a group with optics experts means I have access to various advanced microscopes and special tools built in our lab, which is an invaluable asset and an interesting collaboration,” Chan says.
With their help, she has used Photoactivated Localisation Microscopy (PALM) to visualise cell ultrastructure, selective plane illumination microscopy (SPIM) to visualise live samples, laser nanosurgery to dissect sub-cellular structures, and optical tweezers and atomic force microscopy to investigate forces in tissues.
Biology has become an incredibly competitive field. The infamous pressure to publish is higher for academics and those hoping to obtain funding for research, and new standards for research also demand high-quality data, which requires huge quantities of data and funding to sustain the high technological demand.
Fortunately, Chan’s field of cell and tissue mechanics has long been multidisciplinary, with biologists, physicists, and mathematicians working together to understand cell dynamics and how they form tissues and drive development in animal models.
“Science is not as absolute as people might think,” she remarks, “I definitely don’t think there are no more questions to be asked! Technology and research keeps unlocking new levels of inquiry.”
Mentorship
Another issue Chan wants to raise in Biology and Science in general is the underrepresentation of women in science.
"The reasons for this underrepresentation are complex and have been extensively and widely discussed," Chan says, "The science community is increasingly aware of the problem and some governmental bodies, industrial settings, and research funding agencies do respond by giving support to women in the sciences, but more still has to be done!"
Chan credits her Croucher Scholarship with allowing her to build a diverse scientific background in some of the best research institutes in the world, including the Max Planck Institute in Germany and the London Research Institute (now the Francis Crick Institute) in the U.K.
“My mentors and other scientists I was able to work with dedicated their time and energy to solving the mysteries of science purely out of curiosity. Their example helped form my own path and continues to inspire me today,” Chan says.
From her undergraduate study on cell cycles in mammalian cells, Chan moved on to the role of plant chemicals in cancer prevention, control of cell division, tissue growth, and now cell pattern formation during development.
This journey gave her a strong foundation in molecular, cell and developmental biology, which she has been able to transpose into newer technologies and applications, including more physics-related research and advanced microscopy.
“It’s important to keep moving to keep up with science,” Chan muses, “Fruit fly eyes are pretty, but sometimes I think about how I can apply my knowledge to human cells, perhaps in cancer biology to see what controls cancer cell behaviours at the molecular level using multidisciplinary approaches.”
Dr Eunice Chan completed her undergraduate study in Biochemistry at the Hong Kong University of Science and Technology and received her M.Phil degree in Biochemistry at the Chinese University of Hong Kong. Chan followed this with a postdoctoral position at the London Research Institute in UK, and is currently a research fellow at the Developmental Biology Institute of Marseille-Luminy. Chan received a Croucher Scholarship for study as a doctoral student at the Max Planck Institute of Biochemistry in Germany in 2002.
To view Chan's personal Croucher profile, please click here.