"Recreating the kidney from pluripotent cells or somatic cells: progress to date" to be presented by Professor Melissa Little from IMB Kidney Research Laboratory at The University of Queensland.
TIME: 04:00 PM – Tuesday 3 June 2014 (Refreshments follow on Level 5 at 5.00pm)
VENUE: Level 5 Seminar Room, Melbourne Brain Centre, Parkville Campus
ABSTRACT: In the kidney, the cap mesenchyme is the embryonic progenitor population responsible for giving rise to all cell types of the adult nephron, with the exception of the ureteric epithelial-derived collecting ducts. Derived from the metanephric mesenchyme, these nephron progenitors surround the tips of the branching ureteric tree epithelium throughout embryonic development. The progenitor cells express a transcriptional regulatory network that enables the cap mesenchyme to both self-renew and give rise to differentiated daughter cells that form the nephrons. Nephron induction, which occurs via a Wnt-mediated mesenchyme-to-epithelial transition, ceases just after birth in mice, at around postnatal day 3 (or weeks 36-38 of gestation in humans) and this terminal differentiation exhausts the remaining progenitor population. Consequently, after this time, neo-nephron formation is not possible. We have taken three approaches to recreate the nephron progenitor population; i) direct differentiation from human embryonic stem cells via the addition of growth factors, ii) dedifferentiation of adult proximal tubular cells via re-expression of key transcription factors and iii) partial reprogramming of embryonic mouse fibroblasts using the Yamanaka factors. The progress to date and challenges in progressing forward will be discussed.
BIOSKETCH: Professor Little is an NHMRC Senior Principal Research Fellow and leads the Kidney Research Laboratory at the Institute for Molecular Bioscience, The University of Queensland, where she is Head of the Division of Molecular Genetics and Development. Throughout her career, Professor Little’s achievements have been recognized by awards including the GlaxoSmithKline Award for Research Excellence (2005), the Australian Academy of Sciences Gottschalk Medal in Medical Sciences (2004) and an Eisenhower Fellowship (2006). From 2007-8 she was the Chief Scientific Officer of the Australian Stem Cell Centre. Professor Little was member of the Strategic Review of Health and Medical Research (McKeon) Review expert panel, which delivered its 10-year strategic health and medical research plan for the nation to the Australian Government in 2013.
Professor Little received her Bachelor of Science with Honours at the University of Queensland in 1984 and was awarded the University Medal. She completed her PhD, investigating the molecular aetiology of nephroblastoma and other childhood tumors, at the University of Queensland in 1989. Professor Little was initially a cancer geneticist, studying the genes and pathways that lead to the formation of Wilm’s Tumor, first at the MRC Human Genetics Unit of Western General Hospital in Edinburgh, in Scotland from 1990-92 followed by her return to the University of Queensland in Brisbane in 1992. She became a Project leader in 1995, and since then, Professor Little’s research has focused on the molecular basis of kidney development, renal disease and repair.
Professor Little has over 140 publications in high impact journals including Science, Nature Genetics, Nature Cell Biology, Cell Stem Cell, Cell Developmental Cell, PNAS, JASN and Development. She is internationally recognised both for her work on the systems biology of kidney development and for her pioneering studies into potential regenerative therapies in the kidney. Her work has encompassed the characterisation of adult stem cells in the kidney as well as analyses of the embryonic progenitor population. More recently, her work on the developing kidney has driven studies into the recreation of nephron stem cells via the transcriptional reprogramming of adult cells and the directed differentiation of human stem cells into kidney organoids.