Human embryonic stem cells are defined by their ability to differentiate into the hundreds of cell types that populate the human body. The goals of this Stream are to understand the events that direct pluripotent cells along specific pathways of differentiation; and to discover how these events can be modulated and turned to clinical advantage, for example by developing reporter lines of cells for use in drug screening and toxicity testing.
The Stream consists of a set of core modules comprising the laboratories that specialise in the generation of progenitors and differentiated cells that will be distributed to and used by ‘peripheral’ modules for two types of study:
(i) comparison of the properties of hESC-derived progenitor and differentiated cells with their normal adult counterparts. Such comparative studies are essential prerequisites for the use of laboratory derived cells in clinical, commercial and academic settings.
(ii) elucidation of the events that characterise particular cell lineages. In addition there will be close collaboration with researchers in the Stream 2, who will use iPS technology to develop pluripotent stem cell lines.
The long-term goal of the Stream is to generate cells for transplantation therapy. Although the achievement of this goal may lie some years in the future, the work to be carried out by the members of this Stream within the next two years will provide the critical underpinning required for eventual success.
There is considerable opportunity for interaction and collaboration across modules. Achievement of the aims of Module 1 will involve some degree of collaboration with all modules in the Stream. In particular, work on the formation of haematopoietic mesoderm fits with Modules 3 and 7, the generation and characterisation of haematopoietic stem cells shares common interests with Modules 6 and 7 and the culture and expansion of definitive erythroid and neutrophil progenitor cells ties in with Module 2 and also Collaborative Stream 1, Module 4.
The expected outcomes for this Collaborative Stream is to produce unlimited sources of human progenitor and mature cells relevant to both normal development and disease models; generate reporter lines valuable for screening programs which will facilitate the identification of small molecule alternatives to the expensive and often closely held growth factors; and provide mature cells of value to academia and pharma for screening efficacy and tolerability of lead compounds.
Stream Leader: Professor Andrew Elefanty
Professor Andrew Elefanty is the Joint Laboratory Head of the Embryonic Stem Cell Differentiation Laboratory of the Monash Immunology and Stem Cell Laboratories.
The laboratory has focused on human embryonic stem cell differentiation along mesodermal (blood, endothelium and heart) and endodermal (pancreas) lineages. The group has made significant contributions to the field in the culture of human embryonic stem cells, and they have developed a robust system for the efficient differentiation of human embryonic stem cells, complemented by the development of a safe animal product free medium in which human embryonic stem cell differentiation can be reproducibly directed to different lineages by the inclusion of specific growth factors. The group has generated genetically modified human embryonic stem cells lines in which fluorescent reporters have been introduced into key gene loci that allow objective monitoring of in vitro differentiation of embryonic stem cells in a logical, step-wise fashion.
Deputy Stream Leader: A/Professor Susie Nilsson
In July 2009 Associate Professor Susie Nilsson (nee Begg) joined CSIRO Molecular and Health Technologies but along with her team remains based in the ASCC laboratories. Prior to this, Associate Professor Nilsson was the head of the Niche Laboratory at the Australian Stem Cell Centre having moved from the Peter MacCallum Cancer Centre at the end of 2005, where she was head of the Microenvironment Laboratory within the Stem Cell Program.
Associate Professor Nilsson’s underpinning scientific objective has been to characterise the haemopoietic stem cell niche. She developed an in vivo cell tracking model to identify haemopoietic stem cells (HSC) in situ and was one of the first investigators to provide convincing evidence that HSC preferentially seek and reside within the endosteal region of the bone marrow.
Associate Professor Nilsson is the author of 45 publications, including 32 in the past 10 years. During this time she has been invited to submit five peer reviewed papers and five book chapters.
In the past decade, she been awarded six patents, all of which are at various stages from provisional applications to national phase. She is currently a member of the Board of Directors of Experimental Haematology and a member of the International Society for Stem Cell Research.