John Monash Scholar Owen Siggs, currently completing a joint PhD/DPhil at The Scripps Research Institute, La Jolla, USA and Oxford University, UK is the lead author of a ground-breaking paper on the genetic determinants of white blood cells. The paper, titled "The P4-type ATPase ATP11C is essential for B lymphopoiesis in adult bone marrow", was published online this week in the high-impact scientific journal Nature Immunology. An independent study by researchers at the Australian National University, published in the same journal, supports the La Jolla group's findings.
Nature Immunology's press release stated: "An X-chromosome linked gene mutation that affects the development of antibody-producing B cells in the bone marrow is identified in two independent studies published online this week in Nature Immunology. Deciphering how the pathway for the mutation works may explain some inherited B cell deficiencies that affect males and could likewise provide a potential novel target for some B cell malignancies. Chris Goodnow (from the Australian National University, Canberra), Bruce Beutler (The Scripps Research Institute, La Jolla, CA, USA), and their respective colleagues looked at chemically mutagenized mice with random single gene mutations, finding male mice with defective B cell generation. Beutler’s group shows this defect affects B cell generation in adult bone marrow but not in fetal liver. They trace the defect to the Atp11c gene, which encodes a protein that ‘flips’ particular membrane phospholipids from the facing outside to the cell interior. Lack of this protein is sufficient to doom the developing B cells; hence fewer cells emerge from the bone marrow and result in lower antibody production in response to infections. These findings suggest membrane phospholipid asymmetry somehow regulates B cell generation in the bone marrow context."
The papers describe a gene present in all of us, but whose function was previously not understood. This gene (called Atp11c) encodes a protein that is required for the development of B cells: a type of white blood cell that helps protect from infection. B cells can also contribute to autoimmune disease, leukemia and lymphoma. Knowledge of the function of ATP11C might one day reveal useful new drug targets.
The parallel studies illustrate the important role Australian researchers are playing in understanding our genes, in particular genes that shape our immune systems. Owen's role as lead author reflects a considerable contribution to research in the field. Since starting his studies at The Scripps Research Institute, Owen has identified new functions for several genes, and coauthored multiple peer-reviewed publications. Professor Chris Goodnow at ANU, senior author of the second paper and also Owen's former mentor, was elected as a Fellow of the UK Royal Society in 2009, for his pioneering work using molecular genetics to reveal key regulators of the immune system.
Owen is currently preparing to transfer his study to Oxford in September, where he will complete his DPhil by 2013.