ABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Alexandra Fletcher-Jones is first author on ‘ SGIP1 binding to the α-helical H9 domain of cannabinoid receptor 1 promotes axonal surface expression binding’, published in JCS. Alexandra is a Senior Research Associate in the lab of Jeremy Henley at the University of Bristol, UK, investigating subcellular trafficking of cannabinoid receptor 1 (CB1R).
Alexandra Fletcher-Jones
How would you explain the main findings of your paper in lay terms?
Cannabis has been used as a medicinal herb for at least 4000 years, and it is well established that it has beneficial effects, such as providing pain relief and treating epilepsy. Specific chemicals in cannabis work by activating a protein in the brain called cannabinoid receptor 1 (CB1R) that is part of a complex network of proteins called the endocannabinoid signaling system (ECS). The role of the ECS is to dampen down brain activity by reducing the amount of neurotransmitter released at synapses, which are the connections between nerve cells. This is an important feedback loop that prevents synaptic activity from going out of control and damaging the brain by causing nerve cell death.
Despite its importance, little is known about how CB1R is sent to, and kept at, the section of the nerve cell where it needs to be to work properly. Here, we show that another protein called SGIP1 binds to CB1R to hold it in the correct place. When SGIP1 is removed, CB1R is less stable and the downstream effects of CB1R are reduced. This is important because understanding how CB1R is regulated in the brain can help us to develop better cannabinoid-based drugs for treating a wide range of diseases.
Were there any specific challenges associated with this project? If so, how did you overcome them?
Primary neuronal cultures always pose a challenge as they are particularly finicky cells, but they're worth it for their physiological relevance and the beautiful confocal images they produce.
Why did you choose Journal of Cell Science for your paper?
Journal of Cell Science is a well-respected, rigorous community journal that publishes high-quality research in the field of cell biology, so we are delighted to publish this work in JCS.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
I am hugely grateful to my PI, Jeremy Henley, and the senior postdoc in the lab, Kevin Wilkinson (who is now a PI of his own lab!) for their support. Their belief in me and their willingness to give me free rein to pursue my own interests have truly built my confidence in myself as a researcher.
Fluorescence staining of a primary hippocampal neuron transfected with GFP–CB1R. Total GFP–CB1R (shown in green) is present throughout the neuron, whereas surface CB1R (shown in magenta) is restricted to the axon as identified by ankyrin G labelling (shown in red). Untransfected neurons can be seen in the background labelled with somatodendritic marker MAP2 (blue).
Fluorescence staining of a primary hippocampal neuron transfected with GFP–CB1R. Total GFP–CB1R (shown in green) is present throughout the neuron, whereas surface CB1R (shown in magenta) is restricted to the axon as identified by ankyrin G labelling (shown in red). Untransfected neurons can be seen in the background labelled with somatodendritic marker MAP2 (blue).
What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?
Science was always my favorite subject in school, and when I started university, I knew I wanted to major in something in the field of biology, but I wasn't sure what. My very first semester, I took an ‘Intro to Neuroscience’ class, and I was hooked!
One of the most interesting, and quite surreal, experiences I've had recently that reaffirmed my love of science, was going to the 72nd Lindau Nobel Laureate Meeting where I got to chat with inspiring Nobel Laureates such as Martin Chalfie, Ada Yonath and Emmanuelle Charpentier.
Who are your role models in science? Why?
My role models are all the women in science past and present who have led the way and who continue to support one another.
What's next for you?
I am planning on starting to move towards independence by applying for fellowships to eventually run my own lab (wish me luck!).
Tell us something interesting about yourself that wouldn't be on your CV
I have lived in ten cities, in six countries, in three continents.
Alexandra Fletcher-Jones’s contact details: University of Bristol, School of Biochemistry, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK. E-mail: [email protected]
