Nicholas Huntington-Projects

Nicholas Huntington-Projects

Projects

Regulation of innate lymphocyte homeostasis

This project is aimed at understanding how interleukin (IL)-15 regulates homeostasis of NK cells. We have previously shown that IL-15 drives proliferation and up-regulation of NK cell survival proteins while suppressing pro-apoptotic proteins at both a transcriptional and post-translational level in vitro. Despite this, we have very limited understanding of how apoptosis regulates NK cell homeostasis in vivo. Using the latest genetic approaches this project will systematically dissect the requirement for the individual pro- and anti-apoptotic genes in NK cell development, homeostasis and anti-viral/cancer responses in vivo.

Immune cell discovery could help to halt cancer spread

Team members: Rebecca Delconte and Dr Priyanka Sathe

Human xenograft models of lymphoid cell development

Advances in areas of medicine such as genetic therapies, drug and vaccine development, stem cell transplantation and immunotherapy have been hinder by the lack of robust, reproducible, cost effective human model systems. We aim to generate a novel human xenograft model and define the practicalities of such a model in addressing fundamental questions in human haematopoiesis. Our current knowledge of the early steps in human blood cell diversification and differentiation is hindered by difficulties in accessing disease-free haematopoietic tissue and lack of adequate assays and tools. We recently generated a reproducible xenograft system to model healthy human blood cell development, identify novel human haematopoietic progenitor populations, and characterise their transcriptome, growth requirements and differentiation potential. We aim to generate a road map of early human haematopoiesis and will aid our understanding of the cause and consequences of errors in this process that lead to diseases such as chronic infections, leukaemia and immunodeficiencies.

Team member: Dr Priyanka Sathe

De-differentiation of committed cells into haematopoietic stem cells by the instructive role of the transcription factors

Haematopoietic stem cells (HSC) are widely used clinically but their low abundance in individuals and reliance on sufficient donors severely limits their use. Thus, strategies for inducing expansion of HSC or the generation of repopulating HSC from alternative sources are highly desirable. Certain transcription factors have the potential to instruct differentiating embryonic stem cells to generate HSC that can be expanded in vitro, while maintaining long-term engraftment potential. This project will investigate whether these transcription factors can override the lineage commitment process in cells that have already committed to either the lymphoid or myeloid lineage and have lost their long-term self-renewal ability.

Team members: Dr Sebastian Carotta and Dr Milon Pang