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SEMINAR: Making useful human retina in vitro

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Today's date is Thursday, February 25, 2021
Making useful human retina in vitro : School of Human Sciences (APHB) Seminar Series Other events...
The Seminar: A major goal in the stem cell field has been to generate human somatic tissues in vitro which closely represent their native counterparts in both structure and function. Such tissue represents an incredibly useful tool for the study of human development and disease, drug development, or as a source of transplantable tissue for patients suffering from disease or injury. Great efforts have been made to differentiate human pluripotent stem cells towards retinal tissue for ophthalmic research. Incredible advancements in this field over the past 5 years have demonstrated that optic cup morphogenesis can be orchestrated from human pluripotent stem cells in vitro. The resulting tissue, termed ‘retinal organoids’, contain multiple retinal phenotypes which are organised into a retinal-like cytoarchitecture, akin to the native developing human retina. Guided by this work, novel findings are already being disseminated, yet the numerous retinal induction protocols which exist still remain variable in their efficiency and are not yet able to produce morphologically or functionally mature retinal tissue. More consistent methods which yield retinal organoids with high frequency and minimal interorganoid variation, from which retinal phenotypes exhibiting mature features are born, is desirable for the expedient study of retinal development, disease and regeneration. In this seminar I will describe the research I have been doing over the past 9 years which has focused on the production of retinal tissue from human pluripotent stem cells. I will also discuss my most recent work which shows that the method of embryoid body formation employed at the onset of differentiation greatly influences the retinal differentiation potential of human pluripotent cells.

The Speaker: Dr Carla Mellough was born in Scotland and emigrated to Perth as a child. She was educated at The University of Western Australia, where she continued to study her PhD in E/Prof. Alan Harvey’s Neuroscience Laboratory. Her PhD focused on the functional restoration of retinal circuitry in animal models of inner retinal degeneration, by the intraocular transplantation of neural progenitor cells. This work demonstrated that the behaviour of transplanted cells can be influenced by cellular pre-treatment, the microenvironmental changes surrounding apoptosis and timing of transplant. Following her PhD, Carla moved to Durham University in the UK to commence a Research Associate position in Prof. Stefan Przyborski’s Stem Cell and Developmental Neuroscience team. There her research examined the effect of myelin-associated glycoprotein pathway components on adult neural progenitor populations, and how these might impact upon endogenous central nervous system repair. This work revealed that, unlike their developmental counterparts, adult-derived neural progenitors are susceptible to myelin inhibition of neuritogenesis during differentiation, and that this can be overcome by targeting specific signalling pathways. Dr Mellough then accepted a Senior Research Associate position in Prof. Majlinda Lako’s Stem Cell Group at Newcastle University, UK, to focus on photoreceptor production from human pluripotent stem cells. Dr Mellough continued to work with Prof. Lako for 9 years, of which 2 years were spent at the Centro de Investigación Príncipe Felipe in Valencia, Spain, gaining experience in human pluripotent stem cell expansion, characterisation and retinal differentiation. During this time, Dr Mellough established protocols for the production of photoreceptors and retinal pigmented epithelium from human pluripotent stem cells. Her research also identified an important role for Insulin-like growth factor-1 in human eye formation. More recently, Carla has developed a highly efficient in vitro protocol for the generation of three-dimensional laminated human retinal tissue reminiscent of the developing optic cup in utero. These ‘retinal organoids’, made entirely in the laboratory from human pluripotent stem cells, represent a useful in vitro platform for the study of human retinal development and disease. Dr Mellough has recently returned to Perth as the recipient of an independent Brian King Post-Doctoral Fellowship, based at the Lions Eye Institute in Nedlands. In her new role, her research is focused on improving upon the maturity and functional capacity of the human retinal organoids that we are currently able to achieve, in order to develop a more broadly applicable in vitro platform for interrogation. Additionally, by using cells obtained from patients affected by inherited retinal disease, she will directly study patient-derived retinal organoids in order to mine biological mechanisms underlying specific forms of visual loss that have not yet been studied in the human setting.
Speaker(s) Dr Carla Mellough, Brian King Post-Doctoral, Fellow Harry Perkins Institute for Medical Research
Location Seminar room 1.81 (first floor) Anatomy building, The University of Western Australia
Contact Deborah Hull <[email protected]> : 6488 3313
URL https://www.aphb.uwa.edu.au/research/seminars
Start Tue, 28 Mar 2017 13:00
End Tue, 28 Mar 2017 14:00
Submitted by Deborah Hull <[email protected]>
Last Updated Tue, 07 Mar 2017 12:00
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