Prof Oliver Blacque and Ms Ailís Moran, University College Dublin
Commencing in 2019, this 3-year project is co-funded by Fighting Blindness and the Irish Research Council (IRC) under the IRC Enterprise Partnership Postgraduate Scheme. Through this study, Prof Blacque and Ph.D. student Ailís Moran aim to unearth important fundamental cilia biology relevant to ciliopathy diseases. We spoke with Prof Blacque to learn a little more.
Can you tell us a little more about your research project?
A few years ago, through studying the ‘eyeless’ nematode worm (C. elegans), our lab discovered that that a protein called Rab28 operates in a type of cilia called the primary cilia. Since then, we and others groups have shown that, in mice and zebrafish, this Rab28 protein functions in the photoreceptor cell’s outer segment (modified cilium). Cilia are slender, microscopic, hair-like structures that extend from the surface of nearly all mammalian cells, including retinal cells.
They act like microscopic train-tracks, and allow the transport of vital molecules from one end of the photoreceptor to the other. Dysfunction or defects in cilia are now understood to underlie a number of genetic forms of retina conditions such as cone-rod dystrophy, Usher syndrome, Bardet-Biedel syndrome and Alström Syndrome. Collectively, these are termed ciliopathies. However, despite progress, we still know very little about what exactly Rab28 is doing in cilia, how its function relates to ciliopathy proteins, and how its disruption causes blindness.
This project aims to increase our understanding of Rab28 and potential role in cone-rod dystrophy. In addition, together with Fighting Blindness, this project will develop patient-oriented strategies towards greater public awareness and engagement of ciliopathy-related IRDs.
What attracted you to retinal research?
During my postdoctoral research, I worked on a ciliopathy disorder called Bardet-Biedl syndrome (BBS). Thus, from the outset, I was interested in the role that cilia play in the retina. On arriving at UCD, there were a number of groups there studying retinal research which again encouraged me.
Retinal research is also particularly attractive to me because of the emerging notion that therapeutic endpoints can be achieved by uncovering the secrets of cilium biology.
Within the next five years, where do you expect great advances to be made in vision research?
Gene editing techniques that precisely engineer patient mutations in animal models represents a paradigm shift towards better understanding of disease mechanisms and routes to therapy.
What are your other interests?
I am broadly interested in understanding the fundamental mechanisms by which primary cilia are built and maintained, including how molecular barriers at the base of cilia control the entry and exit of molecules into the structure.
This project is now completed and below is the list of publications that have come from it:
- Sundaramurthi, H., Moran, A., Cerquone Perpetuini, A., Reynolds, A., and Kennedy, B.N., Emerging Drug Therapies for Inherited Retinal Dystrophies. Adv Exp Med Biol. Vol. 1185 (43), 2019. Click here to find the full information about this study.
- Akella, J.S., Carter, S.P., Rizvi, F., Nguyen K.C.Q,. Tsiropoulou, S., Moran, A.L., Silva,M., Kennedy, B.N., Hall, D.H., Barr, M.M. & Blacque,O.E., A ciliary BBSome-ARL-6-PDE6D pathway trafficks RAB-28, a negative regulator of extracellular vesicle biogenesis. eLife, 2020. Click here to find the full information about this study.
Carter, S.P., Moran A.L, Matallanas D, McManus GJ, Blacque OE, Kennedy BN. Genetic Deletion of Zebrafish Rab28 Causes Defective Outer Segment Shedding, but Not Retinal Degeneration. Front Cell Dev Biol. Mar 17;8:136. Click here to find the full information about this study.
- Sundaramurthi,H., Roche, S., Grice, G.L., Moran, A.L., Dillion,E., Nathan, J., & Kennedy, B.N. , Selective Histone Deacetylase 6 Inhibitors Restore Cone Photoreceptor Vision or Outer Segment Morphology In Zebrafish And Mouse Models Of Retinal Blindness. Front Cell Dev Biol. Aug 26;8:689. Click here to find the full information about this study.
- Moran, A.L, Carter S.P., Kaylor J.J, Jiang Z, Dillon E.T, Minhas SJ, Gomez Sanchez A, Carey M, Radu R.A, Travis G.H, Blacque O.E, Kennedy B.N,. Dawn And Dusk Peaks Of Outer Segment Phagocytosis, and Visual Cycle Function Require Rab28 FASEB J. 2022;00:e22309. Click here to find the full information about this study.
- Moran, AL, Fehilly, JD, Floss Jones, D, Collery, R, Kennedy, BN. Regulation of the rhythmic diversity of daily photoreceptor outer segment phagocytosis in vivo. The FASEB Journal. 2022; 36:e22556. Click here to find the full information about this study.
- Emma R. Dorris E.R; Grealis S; Kegl K; Kennedy N; Kramer A; Larkin A; Lynch B; Moran A.L; O’Brien J; Skeffington S; Slater K; Ward R. Priorities for rheumatic and musculoskeletal disease research in Ireland BMC Rheumatol 6, 55 (2022). Click here to find the full information about this study.
- Ailis L. Moran, Stephen P Carter, Joanna J Kaylor, Roxana A Radu, Alicia Gómez Sánchez, Gabriel H Travis, Oliver E. Blacque, Breandan N Kennedy; Deciphering the role of Rab28 in cone vision and outer segment phagocytosis. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2978. Click here to find the full information about this study.
- Ailis L. Moran, Eugene Dillon, Michelle Carey, Oliver Blacque, Breandan N Kennedy; Elucidating Intrinsic and Extrinsic Regulators of Outer Segment Phagocytosis in Zebrafish. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1904 – A0050. Click here to find the full information about this study. Click here to find the full information about this study.
- Ailis L. Moran, Justine O’ Brien, Breandán N. Kennedy, UCD Inherited Blindness Summer School 2021 Br J Pharmacol. 2021 Dec;178(24):4923-5006. Click here to find the full information about this study.
- Ailis L. Moran, Rebecca Ward, Breandán N. Kennedy, UCD Inherited Blindness Summer School 2019 Br J Pharmacol. 2020 Jun;177(11):2487-2654. Click here to find the full information about this study.