Stem cells of all kinds respond to specific changes in their environment by dividing and/or by changing their patterns of gene expression so that they can carry out specific functions in the body. In recent years, many of the environmental signals that guide stem cells along these pathways of differentiation have been identified and many of the mechanisms that they use to turn target genes on and off are now understood.
If stem cells are to be used for first line therapeutic purposes, for example, as sources of red blood cells or as cellular treatment for immune deficiencies – it will be necessary to find ways to grow them in large numbers and large volume and to guide their differentiation along the appropriate pathways. A major goal of Collaborative Stream 1 is to design, test and validate artificial surfaces that (i) recreate natural cell-cell and cell-surface interactions that can be mass produced and used to generate the huge numbers of cells that will be needed to treat patients. In addition, researchers in Collaborative Stream 1 will design, synthesise and test small molecules that can be added directly to media in bioreactors that can be used to grow particular types of stem cells and their differentiated products in large volumes.
Much of the research proposed in Stream 1 is directed toward the discovery and development of products and processes to improve the growth and controlled differentiation of stem cells. In the shorter term, the program will develop fully defined substrates and media that allow controlled, reproducible conditions for growth and differentiation of a variety of cells. In the longer term, the research will provide the defined, safe, scalable conditions essential for the use of stem cells in the clinic.
Collaborative Stream 1 displays multidisciplinary expertise across the six modules and covers the overlapping areas of biomaterials, cellular and molecular biology and the development of bioprocesses. The module is divided into two main programs (i) the growth and differentiation of human embryonic stem cell (hESCs) via the use of novel smart surfaces and media and (ii) the differentiation of haemopoietic stem cells (HSCs) to produce neutrophils, red blood cells and megakaryocytes.
Modules 2, 5 and 6 share common themes in the hESC growth and differentiation through the development of defined surfaces and media capable of supporting pluripotent hESC growth; interplay between soluble factors and attached factors, and the development of suspension processes for accurate monitoring and control of conditions for hESC growth. While modules 1, 3 and 4 share common themes in the HSC program including haemopoiesis; expansion of HSC; biomanufacturing of neutrophils, red cells and platelets; smart surfaces and immobilised ligands.
This Stream also has the potential to directly benefit from discoveries made in the three other Collaborative Streams. Improvements in differentiation of hESCs, knowledge gained about the control of the stem cell niche or the generation of new sources of pluripotent stem cells would all feed directly into and strengthen Collaborative Stream 1.
Stream Leaders: Professor Peter Gray
Professor Peter Gray was appointed in 2003 as the inaugural Director of the Australian Institute for Bioengineering and Nanotechnology (AIBN) at the University of Queensland. Professor Gray was Professor of Biotechnology at the University of New South Wales, and was Director of the Bioengineering Centre, UNSW and Senior Principal Research Fellow at the Garvan Institute of Medical Research. He has held academic positions at University College London and at the University of California, Berkeley. Professor Gray has had commercial experience in the USA working for Eli Lilly and Co and the Cetus Corporation.
Professor Gray is a Fellow of the Australian Academy of Technological Sciences and Engineering, the Australian Institute of Company Directors, and the Institution of Engineers Australia. He was one of the founders and is a past President of the Australian Biotechnology Association (AusBiotech). Professor Gray serves on the Boards of Biopharmaceuticals Australia Pty Ltd, ACYTE Biotechnology Pty Ltd and the Advanced Water Management Centre, and on a number of government committees in the fields of biotechnology, pharmaceuticals and education. He is a regular reviewer and consultant for public and private sector research initiatives in Australia and overseas.
Deputy Stream Leader: A/Professor David Haylock
A/Professor David N Haylock has extensive knowledge and expertise in the biology of human haemopoietic stem and progenitor cells. He made the initial observation that haemopoietic recovery following high dose induction chemotherapy for acute myeloid leukaemia was associated with a dramatic increase in the level of circulating haemopoietic progenitor cells. In collaboration with Drs Juttner and To, he pioneered autologous transplantation with mobilised blood progenitor cells, a technique that has since revolutionised haemopoietic transplantation. During the last decade, A/Professor Haylock has focused on ex vivo manipulation of haemopoietic stem and progenitor cells for therapeutic purposes.
From 2000-2005, as Head of Experimental Cell Therapy at the Peter MacCallum Cancer Centre, A/Professor Haylock lead Australia’s first clinical trial with ex vivo expanded CD34+ cells in the setting of repetitive high dose chemotherapy for metastatic breast cancer. He was appointed as the Director of the Major National Research Facility Division of the ASCC in 2004 and continues to participate in fundamental research on haemopoietic stem cells and the haemopoietic stem cell niche in collaboration with A/Professor Susie Nilsson. In July 2009 A/Professor Haylock joined CSIRO Molecular and Health Technologies, but with his team has remain based in the ASCC laboratories.