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Melissa Little

Professor Melissa Little is a scientist known for her work on the development of the kidneys, and mechanisms of disease and repair. Most recently she is renown for developing an organoid 'Kidney in a Dish[1]' system - a term used by the media to explain organoids, a simplified set of self-organising cells similar to those found in an organ.

Early life and education

Melissa Little was born in Brisbane, Australia on 5th December 1963, the middle daughter of three girls. Her father, Ian Little, was a soils chemist with the CSIRO Cunningham laboratories. She graduated from Kenmore State High School in 1980. She completed her BSc at the University of Queensland and was awarded 1st Class Honours in Physiology in 1984. Her PhD studies were performed in the laboratory of Professor Peter Smith at the Queensland Institute of Medical Research enrolled through Biochemistry at the University of Queensland (conferred 1990). In 2004 she graduated from the Australian Institute of Company Directors.

Research on kidney development, disease and regeneration

Melissa started her research career in cancer, studying Wilm's Tumour, a childhood kidney cancer. At the beginning of her career, molecular biology was just taking off and Melissa was awarded a Royal Society Endeavour Fellowship to move to the Medical Research CouncilHuman Genetics Unit in Edinburgh to undertake postdoctoral training with Nicholas Hastie. Here she worked on the gene WT1, the gene that is mutated in a subset of Wilm's tumour patients.

When Melissa returned to Australia she continued to work on WT1, but concentrating on its essential role in the normal development of the urogenital system[2]. Her work focusses on the molecular aspects of kidney development, and using that information to inform stem cell biology and regenerative medicine.

The kidneys are vital organs required for removal of waste products and regulation of fluid balance in the body. Your kidneys completely filter your entire blood volume 60 times a day and reclaim >99% of all fluid filtered. Microscopic tubules called nephrons carry out the filtration of the blood, reclamation of amino acids, nutrients, water and solutes and the concentration of the urine. A human kidney contains on average 1,000,000 nephrons and all these nephrons arise before birth. Using the more than 20 years of research understanding normal kidney development, Melissa and her team have developed an approach to recapitulate nephrogenesis in a dish. By knowing where the different kidney cells come from and how they develop she has developed a system to regenerate them from pluripotent stem cells. Using embryonic stem cells, or induced pluripotent stem cells from a patient, her group has described a cocktail of growth factors that can drive development into kidney cells. This process results in the formation of the diverse set of cells required to form a nephron. Using a system of adding and removing different growth factors at different times, the cells that arise self organise to form nephrons.

With more optimisation the group were able to develop self organsing organoids 7mm long over 18 days[3][4]. These small balls of cells have differentiated most of the cells that form the kidneys, including collecting ducts, podocytes, vasculature cells, nephrons and loops of Henle, and are closely related transcriptionallly to first and second trimester developing kidneys.

The ability to recreate the early human kidney from stem cells suggests the possibility of one day regrowing a kidney for transplantation. While the science required for this is still a long way off, kidney organoids are hoped to be useful in modeling kidney disease and screening their response to drugs. It is now possible to create stem cells from patients with a genetic disease that affects the kidney. These patient-derived stem cells can then be use to model the kidney of that patient. It is also now possible to edit a mutated gene using the CRISPR/Cas9 system to create a repaired patient stem cell to compare to the original cell. In this way, comparing diseased and gene-corrected kidney organoids will improve our understanding of the role of specific mutations on kidney development and disease. Kidney organoids could also be used in drug screening. Almost one third of all drugs that fail to reach the market do so as a result of toxicity to the kidney [5], and earlier detection of potentially toxic drugs would improve safety in clinical trials.

Contributions to Australian Science policy

Professor Little has contributed to the shaping of Government policy around science, particularly Health and Medical Science, across her entire career. In the late 1990's, she was a member of the Strategic Review of Health and Medical Research, chaired by Mr Peter Wills, AM. This review proposed a Virtuous Cycle between research, government and the commercial sector arguing the case for the research funding based on excellence across the breadth of health and medical research, from biomedical through clinical, public health and health services research. As a result of these recommendations, the budget of the NHMRC was doubled across the ensuing 10 years. Melissa went on to serve on the Implementation Committee of that review and served under Robin Batterham, Chief Scientist, to identify strategic priorities across Australian science, reporting to Minister Peter McGauran. A member of the NHMRC Research Committee for 6 years, she was also a member of the most recent review of health and medical research, chaired by Mr Simon McKeon, which led to the establishment of the Medical Research Future Fund and the Biomedical Translation Fund.

Professional Associations

Melissa Little is the current Program Leader of Stem Cells Australia[6], an organisation that aims to "Bring together Asutralia's premier life scientists to tackle the big questions in stem cell science". She is also a guest editor with the scientific journal Development[7]. She is the serving theme director of Cell Biology[8] at the Murdoch Childrens Research Institute and directs the MCRI Stem Cell Medicine Strategic Priority area. Melissa is also the President of the Australasian Society for Stem Cell Research and a Board Member of the International Society for Stem Cell Research.

Awards and honours[9]

2017, Fellow of the Australian Academy of Science

2016, Fellow of the Australian Academy of Health and Medical Sciences

2016, Eureka Prize for Scientific Research[10]

2015, Boorhaave Professorship, University of Leiden, The Netherlands

2013, Women in Technology Biotechnology and Outstanding Biotechnology Award Finalist

2013, NHMRC Senior Principal Research Fellowship

2006, Smart Women – Smart State Award[11]

2006, Eisenhower Fellowship

2005, GlaxoSmithKline Award for Research Excellence

2004, NHMRC Principal Research Fellowship

2004, Named in The Bulletin Smart 100

2004, Australian Academy of Sciences Gottschalk Medal in Medical Sciences

2002, NHMRC Senior Research Fellowship

1997, Sylvia and Charles Viertel Senior Research Fellowship

1995-8, National Health and Medical Research Council R. Douglas Wright Fellowship

1990-4, Royal Society Endeavour Fellowship (inaugural award)

References

  1. ^ Salleh, Anna (2015-10-08). "Skin cells used to grow mini kidneys in a dish". ABC News. Retrieved 2017-08-29.
  2. ^ Vicente, Catarina (2016-03-15). "An interview with Melissa Little". Development. 143 (6): 907–909. doi:10.1242/dev.135897. ISSN 0950-1991. PMID 26980790.
  3. ^ Takasato, Minoru; Little, Melissa H. (2016-12-15). "A strategy for generating kidney organoids: Recapitulating the development in human pluripotent stem cells". Developmental Biology. The Development of Stem Cell-derived Organoids. 420 (2): 210–220. doi:10.1016/j.ydbio.2016.08.024.
  4. ^ Takasato, Minoru; Er, Pei X.; Chiu, Han S.; Maier, Barbara; Baillie, Gregory J.; Ferguson, Charles; Parton, Robert G.; Wolvetang, Ernst J.; Roost, Matthias S. (2015-10-22). "Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis". Nature. 526 (7574): 564–568. doi:10.1038/nature15695. ISSN 0028-0836.
  5. ^ Perazella, Mark A.; Markowitz, Glen S. (August 2010). "Drug-induced acute interstitial nephritis". Nature Reviews Nephrology. 6 (8): 461–470. doi:10.1038/nrneph.2010.71. ISSN 1759-5061.
  6. ^ "Welcome to Stem Cells Australia". www.stemcellsaustralia.edu.au. Retrieved 2017-08-29.
  7. ^ Vicente, Catarina (2016-03-15). "An interview with Melissa Little". Development. 143 (6): 907–909. doi:10.1242/dev.135897. ISSN 0950-1991. PMID 26980790.
  8. ^ "Cell Biology | Murdoch Childrens Research Institute". www.mcri.edu.au. Retrieved 2017-08-29.
  9. ^ "Professor Melissa Little | Murdoch Childrens Research Institute". www.mcri.edu.au. Retrieved 2017-08-25.
  10. ^ Dean, Tim. "The 2016 Eureka Prizes showcase the best in Australian science". The Conversation. Retrieved 2017-08-25.
  11. ^ "UQ staff and students win four Smart Women Smart State awards". UQ News. Retrieved 2017-09-05.