Research Projects
Lieschke Group projects focus on the development and function of white blood cells. White blood cells are also called “leukocytes” and there are two major types: “granulocytes” or “neutrophils” and “macrophages”. They are important in host defence, are the cellular effectors of inflammation, and are the cell type that grows without control in leukaemia.
Development of white blood cells
To discover new genes that were critical for white blood cell development, a forward genetic screen of chemically-mutated zebrafish collected a group of mutants with defect blood cell development. Characterisation of these mutants and cloning the mutated genes underpinning the phenotypes is ongoing in the group. These mutants point to new critical steps in the genetic and biochemical regulation of blood cell development.
MicroRNAs in blood cell development
One of our mutants had a surprisingly specific defect in expression of a pair of microRNAs important for red blood cell maturation (miR-144/451). We are studying the role of these microRNAs in regulating blood-cell specific genes during their development. We have cloned the defective gene in this mutant and are trying to understand what this is telling us about microRNA biogenesis.
Inflammation
How is the inflammatory response is regulated? While inflammation is important for protecting the body in the face of tissue damage, turning inflammation off is important to minimize unnecessary damage. We are aiming to discover new pathways that initiate and turn off the contribution of white blood cells to inflammation. These studies take advantage of the ability to image inflammation in transparent zebrafish embryos, using trangenic strains with fluorescent white blood cells. They involve sophisticated microscopy and quantitative image analysis.
Infection
An important function of white blood cells is in host defence – keeping out and containing invading micro-organisms. To study this role of white blood cells, we have established a zebrafish model of infection with Penicillium marneffei, an opportunisitic human pathogen. To facilitate these studies, we have made several transgenic lines that enable macrophages, one particular type of white blood cell, to be seen and manipulated.
Regeneration
When a tissue is injured, the outcome of healing can be either scarring or regeneration. White blood cells and the inflammatory response are important determinants of the balanced outcome. We plan to extend our work in inflammation to ask how modulating the inflammatory white blood cells might tip the outcome to favour of regeneration rather than scarring.