FIRST PERSON

First person – Frances Tilley

First Person is a series of interviews with the first authors of aselection of papers published in Journal of Cell Science, helpingearly-career researchers promote themselves alongside their papers.Frances Tilley is the first author on ‘Retromer associates with thecytoplasmic amino-terminus of polycystin-2’, published in Journal ofCell Science. Frances conducted the work in this article while a PhDstudent in the lab of Peter Cullen at the University of Bristol, UK, but isnow a postdoc in Corinne Antignac’s lab at Imagine Institute, Paris,France, investigating the mechanisms of pathogenesis in Galloway–Mowat syndrome, with a focus on the role of podocytes on diseaseprogression.

How would you explain the main findings of your paper in layterms?The environment of a cell has an impact on how that cell behaves, inthe same way that the behaviour of humans and other animals isinfluenced by the circumstances in which they find themselves.Whereas humans have eyes, ears and a nose to sense theirsurroundings, cells instead have to rely on protein ‘sensors’embedded in their outer membrane. These sensors are in a constantstate of flux, as cells will internalise the sensor molecules to relay thesignal to its nucleus (the ‘brain’ of the cell in this analogy) and thenrecycle the sensor back to the membrane where it can be reused.Mutations in proteins that regulate this internalisation and recycling ofcell membrane sensor molecules underlie a number of humandiseases, as it means the cell cannot respond properly to changes in itsenvironment. For example, some cases of autosomal dominantpolycystic kidney disease (ADPKD) are caused by loss of a proteincalled polycystin-2 (PC2) from the surface of a type of kidney cell. Inthis article, we describe a link between retromer, a protein known tobe involved in cell membrane sensor recycling, and PC2, suggestingthat retromer could have a role in the development of ADPKD.

Were there any specific challenges associated with thisproject? If so, how did you overcome them?The challenge in this project was to test our hypotheses in a morephysiologically relevant model system. Our lab has traditionally beenconcerned with the basic cell biological mechanisms of endosomaltrafficking, and we have traditionally used HeLa and retinal pigmentepithelial-1 (RPE-1) cells for our experiments. The initialidentification of polycystin-2 as a putative retromer-interactingpartner, and the immediate implication that retromer could alsohave a role in ADPKD pathology, caused us to seek collaborationwith a lab that was specialised in the sort of physiological assays weneeded to advance the project. Luckily, we were able to establish alink with the Zhou lab at the Harvard Polycystic Kidney DiseaseCenter, who were able to help us enormously by performing PC1ciliary trafficking assays as a read-out of PC2 function in kidneytubule cells.

When doing the research, did you have a particular result or‘eureka’ moment that has stuck with you?My favourite moment of this research project was the first time Ilooked at cells expressing a GFP-tagged PC2 construct that waslacking its carboxy-terminal domain, co-stained for the retromercomponent VPS35. I had hypothesised that perhaps I was not seeingcolocalisation or co-immunoprecipitation between overexpressedfull-length PC2 and retromer because exogenous PC2 was trappedin the ER, but I was still surprised to see how once the ER-retentionsite of PC2 was removed, PC2 became almost totally colocalisedwith retromer-marked endosomes.

Have you had any significant mentors who have helped youbeyond supervision in the lab?My supervisor, Prof. Peter Cullen, was a great mentor throughoutmy PhD. In particular, he helped me see at what point it is worthpursuing hypotheses, at what point it is more productive to move onto something else, and also to be positive about the work I havedone. In addition, my current supervisor, Prof. Corinne Antignac,has helped me to develop confidence in my abilities to direct aresearch project, and to keep in mind what I want as an outcome,particularly as it relates to further understanding a cellular process inthe context of patient interests.

“I met people from all over the world […]and also wanted to work in a field where Iwould both have the chance to travel, andtoworkwith people fromcultures differentto my own.”

Frances Tilley

Frances Tilley’s contact details: Laboratory of Hereditary Kidney Diseases, ImagineInstitute, Necker Hospital, 24 Boulevard du Montparnasse, Paris 75015, France.

E-mail: frances.tilley@inserm.fr

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© 2018. Published by The Company of Biologists Ltd | Journal of Cell Science (2018) 131, jcs220723. doi:10.1242/jcs.220723

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What motivated you to pursue a career in science, and whathave been themost interestingmoments on the path that ledyou to where you are now?I have been motivated to pursue a career in science since I took partin the summer student programme at the Cancer Research UKLondon Research Institute in 2011. Although I have always beeninterested in science, I was totally enamoured by the fact that thepeople I met at the LRI had almost total control over their work, andhad the privilege to work on something that fascinated them everyday, which was also in the interest of improving the lives of people

with cancer. I met people from all over the world at the LRI, and alsowanted to work in a field where I would both have the chance totravel, and to work with people from cultures different to my own.One of mymost interesting experiences in my scientific career so farwas a short internship I did at the Institute of Food Research (nowthe Quadram Institute) in Norwich. I was in the lab performingmicroarray analysis, but the lab I worked in was also carrying out anintervention study, looking at the effects of ‘super broccoli’ oncardiovascular health. I spent a few afternoons in the fields by theinstitute, helping to harvest the super broccoli.

Who are your role models in science? Why?I have to say that my scientific role model is Dr BrittaWeigelt, who Imet during my internship at the LRI. I was inspired by the passionand enthusiasm with which she approached her work ongynaecological cancers, and by her subsequent career progressiontowards a group leader position at the Memorial Sloan–KetteringCancer Center.

What’s next for you?I am currently just over a year into my first postdoc at ImagineInstitute in Paris, where I am working to uncover the mechanism ofdisease in a subset of Galloway–Mowat syndrome (GAMOS)patients. GAMOS is an extremely rare nephrocerebellar syndromeaffecting mostly children, and I am hoping to stay at Imagine for theforeseeable future, working up the results I have into a morecomplete story, and improving my French.

Tell us something interesting about yourself thatwouldn’t beon your CVI recently provided the voice for a tent in a promotional video for achain of French sports shops.

ReferenceTilley, F. C., Gallon, M., Luo, C., Danson, C. M., Zhou, J. and Cullen, P. J. (2018).

Retromer associates with the cytoplasmic amino-terminus of polycystin-2. J. CellSci. 131, jcs211342.

HeLa cells expressing GFP-tagged PC2(1-703) co-stained for theretromer component VPS35.

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FIRST PERSON Journal of Cell Science (2018) 131, jcs220723. doi:10.1242/jcs.220723

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ofCe

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