B lymphocytes are antibody-producing white blood cells that eliminate pathogens such as viruses and bacteria. A range of diseases involve significantly reduced B lymphocyte numbers, and, by the age of 60 (currently more than 20% of the Australian population), the production of B lymphocytes in humans has significantly declined as a result of ageing. People with low B lymphocyte numbers are more susceptible to infection by viruses such as COVID-19 and other pathogens, contributing to their increased morbidity and mortality. Low B lymphocyte numbers in humans also reduces the effectiveness of vaccinations, further contributing to the risk of infection.
The primary site where B lymphocytes are made is in the bone marrow, and a range of non-blood cells (called bone marrow microenvironment cells) help to regulate the different stages involved in the production of B lymphocytes. Each bone marrow microenvironment that supports the distinct stages of B lymphocyte production is unique and some key regulators of B lymphocytes have been identified. Despite this, little is known about the nature of the cell types that form each distinct B lymphocyte bone marrow microenvironment. Furthermore, the reduced production of B lymphocytes due to ageing is known to be accompanied by changes in B lymphocyte bone marrow microenvironments, however, there is little understanding of what these changes are.
In this project, we will use a highly innovative immunofluorescence imaging technology to identify the different B lymphocyte bone marrow microenvironments. We will also determine the changes that occur to these bone marrow microenvironments during ageing. The studies will incorporate a range of different techniques, including innovative multicolour immunofluorescence studies on bone marrow sections, isolation of bone marrow cells from mice, fluorescence-based immunostaining accompanied by fluorescence activated cell sorting (FACS) and molecular biology techniques.
Dr Gavin Tjin
Stem Cell Regulation Laboratory
Investigating the relationship between blood stem cells and bone marrow ‘niches’, to ultimately improve recovery from bone marrow transplant and cancer therapy
The bone marrow is a factory for making our blood, creating billions of blood cells every day. Distinct places (niches) within the marrow support the production of distinct blood cell lineages from stem cells.
Research points to regulation of these niches being key to balancing the different cell types (such as platelets) in the blood. However, the processes controlling this regulation are not known.
Slow blood cell recovery (particularly low platelet count) is common among bone marrow transplant recipients; typically one-third experience slow platelet recovery, which significantly increases their risk of acute bleeding, illness and death. Low blood cell counts can also persist for more than six months after cancer therapy, are life-threatening and are a major reason for delaying further cycles of treatment – significantly contributing to the failure of chemotherapy to control cancers.
Gavin’s project will for the first time apply innovative and advanced seven-colour microscopy imaging to identify niches in healthy mice and identify changes that occur following bone marrow transplant.
“My goal is to determine the relationship between the stem cells and the niche and how they are affected by bone marrow transplant,” says Gavin. “If we can do that, we are a step closer to understanding the factors that regulate these niches, and hence the regulation of blood cell production.”
Dr Gavin Tjin is an expert in light microscopy, a technique which uses visible light to detect tiny objects. Gavin’s passion is using microscopy techniques to solve biological questions – including how cells interact with their environment and how disease and treatment can alter these interactions.
Joining SVI’s Stem Cell Regulation Laboratory in 2017 as a postdoctoral researcher, Gavin has since independently established the institute’s innovative Opal multiplexing microscopy technique. Gavin completed his PhD at Sydney’s Woolcock Institute of Medical Research and is the author of 21 publications.