Bissig, C.

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Serveur académique lausannois

FIRST PERSONFirst person – Christin BissigFirst 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.Christin Bissig is first author on ‘The PIKfyve complex regulates theearly melanosome homeostasis required for physiological amyloidformation’, published in JCS. Christin conducted the researchdescribed in this article while a postdoc in Dr Guillaume van Niel’slab at the Institut Curie, Paris Sciences & Lettres Research University,France. She is now a postdoc in the lab of Andreas Mayer atDepartment of Biochemistry, University of Lausanne, Epalinges,Switzerland, investigating the molecular mechanisms of intracellularmembrane trafficking.How would you explain the main findings of your paper inlay terms?Our skin and eyes are protected against harmful sunlight by adark pigment, called melanin. The production of melanin is aharmful process; therefore, it is confined to a specific place,called the melanosome, within pigment cells. Like in awarehouse, melanin is stored on a scaffold, which is composedof the protein PMEL. However, we still do not understand howthis scaffold is built up within melanosomes. In our work, wefind that a protein complex called the PIKfyve complex controlsthe formation of this scaffold and therefore pigment production.Like a master builder, PIKfyve regulates the import andexport of PMEL building blocks to assure optimal conditionsfor PMEL scaffold assembly. Interestingly, the PMEL scaffoldresembles very much those protein scaffolds that aberrantlyassemble in the brain and cause neurodegenerative diseaseslike Alzheimer’s disease. Thus, future work will showwhether PIKfyve may play analogous roles in scaffoldassembly during disease.Were there any specific challenges associated with thisproject? If so, how did you overcome them?We quickly had good evidence that inhibition of PIKfyveactivity impairs the formation of PMEL fibrils withinmelanosomes. The main challenge was then to find out why.While we knew that fibril formation requires PMEL sorting andcleavage by proteases, the process of fibril assembly remained ablack box. As PIKfyve has crucial roles in lysosome functions innon-specialized cells, we first thought that the observed defect inPMEL fibril formation could arise from lysosomal dysfunctionsthat would impair PMEL proteolysis. However, all our datashowed that lysosome functions are unaffected by PIKfyveinhibition in pigment cells. Thus, we were on the wrong track.We then changed strategy and decided to do electron microscopyexperiments on high-pressure frozen cells to optimally preservemembrane ultrastructure with the hope of seeing morphologicalchanges in endosomes or melanosomes that are induced byPIKfyve inhibition. It worked out, and we found that PIKfyveactivity is required for membrane remodeling of the earliest stageof melanosomes. This experiment brought us back on track andwe could then go on and describe how these morphologicalchanges affect PMEL abundancy and fibril assembly.When doing the research, did you have a particular result or‘eureka’ moment that has stuck with you?As mentioned above wewere for a long time looking for lysosomaldysfunctions, because in the literature PIKfyve is described to acton lysosomes. Thus, all our negative results did not fit with whatwas known. However, when we found that PIKfyve is a majorplayer in early melanosome maturation everything started to makesense. We could then show that PIKfyve plays similar functions inmaturation of melanosomes and lysosomes in specialized and non-specialized cells, respectively. Thus, our findings indicate thatpigment cells employ a conserved mechanism to generate theirspecialized organelles.…when we found that PIKfyve is a majorplayer in early melanosome maturationeverything started to make sense.Why did you choose Journal of Cell Science for your paper?We chose Journal of Cell Science because we wished to publish in ajournal with an excellent reputation and a wide readership with thegoal to spread our findings as broad as possible within the cellbiology community.Christin BissigChristin Bissig’s contact details: Department of Biochemistry, University ofLausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.E-mail: christin.bissig@unil.ch1© 2019. Published by The Company of Biologists Ltd | Journal of Cell Science (2019) 132, jcs230466. doi:10.1242/jcs.230466JournalofCellScienceHave you had any significant mentors who have helpedyou beyond supervision in the lab? How was theirguidance special?Dr Guillaume van Niel was a great and very enthusiastic mentor forthis work. He managed to perfectly find the balance of guiding,while giving me space to work independently. I have learned fromhim that a scientist must be open-minded and courageous enough toalso pursue unconventional ideas.I have learned from [my mentor] thata scientist must be open-minded andcourageous enough to also pursueunconventional ideas.What motivated you to pursue a career in science, and whathave been themost interestingmoments on the path that ledyou to where you are now?My main motivation for pursuing a career in science is my curiosity.I am a very curious person and I wish to understand how natureworks. Since the beginning of my studies, I have been fascinatedabout the molecular mechanisms cells employ to make our lifepossible. Even though research can be very frustrating at somemoments, I really enjoy working as a researcher. I think it is a veryenriching and exciting job that is intellectually challenging, demandscreativity and gives the possibility to learn something new every day.What’s next for you?Since I enjoy working at the bench I moved on to do anotherpostdoc. After working many years with mammalian cells, I am nowdiscovering the ease and power of yeast.ReferenceBissig, C., Croisé, P., Heiligenstein, X., Hurbain, I., Lenk, G. M., Kaufman, E.,Sannerud, R., Annaert, W., Meisler, M. H., Weisman, L. S. et al. (2019). ThePIKfyve complex regulates the early melanosome homeostasis required forphysiological amyloid formation. J. Cell. Sci. 132, jcs229500.Electron microscopy picture of a high-pressure frozen pigment cellshowing enlarged early melanosomes after PIKfyve inhibitor treatment.2FIRST PERSON Journal of Cell Science (2019) 132, jcs230466. doi:10.1242/jcs.230466JournalofCellScience

First person – Christin Bissig

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First person – Christin Bissig

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Serveur académique lausannois