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. Manu Ahmed is first author on ‘ Identification of 30 transition fibre proteins in Trypanosoma brucei reveals a complex and dynamic structure’, published in JCS. Manu conducted the research described in this article while a PhD student in Professor Sue Vaughan's lab at the Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, UK. He is now a postdoctoral fellow in the lab of Sumeda Nandadasa at the University of Massachusetts Chan Medical School, Worcester, MA, USA, investigating the molecular mechanisms of ciliopathies relating to cystic kidney disease and hydrocephalus.
Manu Ahmed
How would you explain the main findings of your paper in lay terms?
Cilia are essential structures that are required for cell signalling and motility. Transition fibres (also called distal appendages) are structures essential for cilium assembly, and variants in genes that encode transition fibre proteins cause diseases called ciliopathies in humans. To date, only a handful of proteins have been mapped to the transition fibre structure. Here, we identified 30 transition fibre proteins in the parasite Trypanosoma brucei, tripling the known number of proteins associated with this structure. We show that transition fibres are complex structures that are dynamic in their protein composition throughout the cell cycle and play essential roles in the assembly and length regulation of cilia.
Were there any specific challenges associated with this project? If so, how did you overcome them?
Transition fibres are small structures only a few hundred nanometres in diameter. We were therefore challenged by the limited resolution of light microscopy. To overcome this, we leveraged the power of automated image analysis and averaging to measure the diameter of each protein in thousands of cells. This allowed us to map 30 new transition fibre proteins and unveil the molecular architecture of these structures in unprecedented detail.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
Observing a severe ciliogenesis phenotype after knocking down a gene with no known function was an exciting moment.
Why did you choose Journal of Cell Science for your paper?
Journal of Cell Science has a history of publishing high-quality cell biology articles, including many relating to the structure and function of cilia.
Expansion microscopy of transition fibres. Cross section and lateral views of transition fibre protein FBF1 labelled by immunofluorescence, showing a 9-fold radial arrangement in cross section and a necklace surrounding the distal end of the basal body in the lateral view.
Expansion microscopy of transition fibres. Cross section and lateral views of transition fibre protein FBF1 labelled by immunofluorescence, showing a 9-fold radial arrangement in cross section and a necklace surrounding the distal end of the basal body in the lateral view.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
Dr Richard Wheeler was instrumental in helping to develop the automated scripts that allowed us to map transition fibres in such volume and detail. Thanks to his expertise and support, this critical aspect of the project was possible.
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?
The unknown has always been innately fascinating to me. As a child, I would imagine early human explorers looking over the next horizon and wondering what lay beyond. Looking under the microscope, I realized the microscopic world is the next horizon to explore. I was always inspired to pursue a career that delves into the unknown and provides an outlet for my curiosity about the nature of the world.
Who are your role models in science? Why?
My grandmother Lindy Castell is my greatest inspiration and role model in science. An immunologist at Oxford, she always nurtured my curiosity for science and guided me towards the direction of research and discovery. She is the biggest influence that has led me to where I am now, and I'm profoundly grateful to her.
What's next for you?
I am currently undertaking postdoctoral research investigating mechanisms underlying ciliopathies. In particular, we are focusing on the role of extracellular matrix proteases in the development of polycystic kidney disease and hydrocephalus.
Tell us something interesting about yourself that wouldn't be on your CV
I am a lifelong jazz and blues pianist, and I frequently play in the bars and restaurants around Oxford.
Manu Ahmed's contact details: University of Massachusetts Chan Medical School, 55 Lake Ave, Worcester, MA, USA.
E-mail: [email protected]
