One of the most challenging experiences of my life was getting started with my PhD at EMBL, to study how organisms develop their shape, a process known as morphogenesis. Trained as a microbiologist, I was used to working with tiny single cells that displayed a rather simple behaviour. In the De Renzis group, I had to deal with fruit fly embryos made of thousands of cells that constantly exchange information and influence each other.<\/p>\n\n\n\n
Understanding what is going on when an organism such as a fruit fly develops from egg to larva is a daunting task. Much of what we know about the biological processes that drive development comes from turning specific genes on and off and then watching for the effect. However, the commonly used techniques have a limitation: one has to wait some time (several hours in the best case) before looking at the consequences of such perturbations and drawing conclusions. As my supervisor Stefano De Renzis puts it, \u201cit\u2019s like arriving at the scene of a car crash: you know something went wrong at some point, but you were not there when it happened, so you cannot tell what exactly<\/em> caused the accident\u201d.<\/p>\n\n\n\n When I joined Stefano\u2019s lab, my dream was to have a remote control to perturb the activity of single cells, and watch the effects immediately. That way, I thought, it would be much easier to understand when and where specific cell behaviours were needed during complex developmental processes. I thought that a feasible way to create such a remote control would be to use light. Back in 1999, Francis Crick had already voiced the possibility of controlling neuron activity with light. Just a couple of years later, neuroscientists managed to use light to activate brain cells, and they named the newborn technique \u2018optogenetics\u2019. However, when I started my PhD in 2011, no one had ever used this technique to interrogate how cells behave and interact with each other in a whole organism during development.<\/p>\n\n\n\n I have always had a strong interest in biotechnology, and introducing optogenetics as a tool to study embryonic development seemed like the ideal PhD project for me. As an embryo develops, most of the changes in its shape are driven by cells contracting, so I decided to prevent them from doing so, by using light to reduce their \u2018muscle fibres\u2019. Work from our and other groups had shown that a particular fatty molecule in the cell membrane \u2013 a lipid called PI(4,5)P2<\/sub> \u2013 serves as an anchor for the fibres that pull on the membrane when the cell contracts, and is essential for many developmental processes. Inspired by these findings, I set up an approach to use light to remove PI(4,5)P2 <\/sub>from the cell membrane, as this would prevent the fibres from latching on, meaning the fruit fly embryo\u2019s cells would be unable to contract. One of the most exciting moments of my PhD was the day I went to the microscope and confirmed that I could stop individual cells from contracting with just a few millisecond pulses of light: my light-based remote control was working!<\/p>\n\n\n