Macrophages and osteoclasts are cells that are critical to the body's ability to repel pathogens, remove damaged tissue and dying cells caused by normal growth and development, as well as decalcify bone. Understanding how these cells function could help boost their normal function and also limit the damage caused in inflammatory and infectious diseases when these cells unleash their destructive capabilities inappropriately.

The research interests of our Laboratory centre on the biology of macrophages and osteoclasts. These are cells of haematopoietic origin that are closely related to each other but have distinctly different activities.

Macrophages are cells of the innate immune system that have critical roles in regulating not only immune response but tissue development and homeostasis.

On the other hand osteoclasts have specialised roles in resorbing bone and in maintaining bone and mineral homeostasis.

The dysregulation of macrophage function mediates several human diseases such as rheumatoid arthritis, inflammatory bowel disease and chronic obstructive pulmonary disease.

The pathological role of macrophages in these diseases is being characterized with the aim of developing novel therapeutic approaches to their treatment.

The bone group led by Dr Ian Cassady focuses on the biology of osteoclasts. These cells mediate the pathology of a number of bone diseases including osteoporosis. The aim is to characterise osteoclast function so that we may be able to manipulate it to yield new treatments of osteoclast-mediated bone diseases.

A central area of our investigations is focused on the mechanisms controlling the differentiation of macrophages and osteoclasts from their progenitors.

Macrophage Colony-Stimulating Factor (CSF-1) is the essential growth factor regulating differentiation, activation and survival of macrophages and osteoclasts. The action of CSF-1 is mediated by its receptor, c-fms, and we have defined the elements within the c-fms gene required for its expression in macrophages thereby identifying lineage-related transcriptional processes. The study of macrophage and osteoclast biology has been facilitated by our generation of transgenic mice bearing the c-fms promotergreen fluorescent protein; the "MacGreen" mice. The macrophages and osteoclasts in MacGreen mice are fluorescently tagged so the cells can be monitored in a living animal. Work is also progressing on development of transgenic mice with macrophage and osteoclast specific, inducible transgenes.

Studying the responses of macrophages to activating signals such as lipopolysaccharide (LPS) and bacterial CpG DNA, has opened new avenues for therapeutic intervention in infectious disease, as well as identifying the novel biology of these cells.

cDNA microarrays are being used to profile global changes in gene expression resulting from macrophage activation by LPS, bacterial CpG DNA and CSF-1 and during osteoclast differentiation and activation. Several novel macrophage/osteoclast specific genes have been identified and are being characterised as part of the structural genomics program, in collaboration with IMB's Jenny Martin and Joint Appointment Bostjan Kobe.