Dr Antje Blumenthal
|Dr Antje Blumenthal|
“If we can understand what is necessary for the body to defeat a pathogen," she says, "then we can focus potential therapies to help that defence. If we identify processes the pathogen requires to establish and maintain an infection, we can target antimicrobials towards these.”
Blumenthal's interest in microbiology began in early high school. She pursued that interest as an undergraduate at the Christian-Albrechts-University in Kiel, Germany, where she became intrigued by the interaction between pathogens and their hosts. She pursued her masters and doctoral research in immunology and infection biology at the Research Centre Borstel, a Leibniz-Centre for Medicine and Biosciences, with a particular focus on tuberculosis (TB).
There, Blumenthal investigated how immune cells, called macrophages, interact and respond to infection with mycobacterim tuberculosis (Mtb) and other pathogenic mycobacteria. Employing the then novel technology of comprehensive gene expression analyses using microarrays in collaboration with collaborators at the German Society for Biotechnology, enabled her to study differences in how the body reacts to mycobacterial strains and species of different virulence. Surprisingly, these studies also revealed genes that had only ever been associated with embryonic development, cell differentiation and cancer, Blumenthal explains. “However, at least one member of this family was found to be well regulated in response to infection. We then showed that it instructed immune cell functions." It was a crucial discovery that has since triggered a new field of study.
In order to gain experience with complex TB infection models, Blumenthal accepted an offer to work with Professors Sabine Ehrt, Carl Nathan and Dirk Schnappinger at Weill Cornell Medical College in New York. There, she discovered a cell surface receptor on macrophages that is required for optimal immune responses and control of TB infection. She believes that small variations in that receptor could contribute to disease severity in individual patients.
Blumenthal also wanted to understand TB from the pathogen’s perspective in order to learn which genes promote establishment of the infection and enable Mtb to persist within the host. She used Mtb mutants that allowed the genetic alteration to be turned on and off at different stages of the infection. Mutation screening was a slow, one-by-one process, so Blumenthal developed a new approach that enabled quantitative screening of multiple regulated mutants at a time.
“Being able to streamline that process, as well as being able to turn mutations on and off during infection, was a big advancement," she says.
Blumenthal then accepted the offer to develop a research program at The University of Queensland Diamantina Institute (UQDI), where her research on the initiation and regulation of immune responses to pathogens fits in well with her colleagues’ research in inflammatory disorders. “We are working on similar questions in different disease settings,” she says.
Blumenthal is now a Balzan Research Fellow at the UQDI and investigates how the immune system recognises pathogens and how immune responses are initiated. She is also researching how biochemical pathways that regulate embryonic development and cell differentiation contribute to the regulation of immune responses during infection. These pathways are currently very attractive drug targets, and understanding their immune functions will help inform decisions relating to the development and use of therapeutics in a variety of disease settings. Blumenthal believes that her work on how immune responses are initiated and regulated will provide knowledge applicable not only to infections but to many inflammatory disorders such as rheumatoid arthritis and diabetes.
“That’s really exciting for me,” she says. “It could contribute to the fundamental understanding of how the immune system works.”
Phone: +61 7 3443 6984
10 Recent Publications
Inder, Kerry L., Ruelcke, Jayde E., Petelin, Lara, Moon, Hyeongsun, Choi, Eunju, Rae, James, Blumenthal, Antje, Hutmacher, Dietmar, Saunders, Nicholas A., Stow, Jennifer L., Parton, Robert G. and Hill, Michelle M. (2014) Cavin-1/PTRF alters prostate cancer cell-derived extracellular vesicle content and internalization to attenuate extracellular vesicle-mediated osteoclastogenesis and osteoblast proliferation. Journal of Extracellular Vesicles, 3 23784.1-23784.14. doi:10.3402/jev.v3.23784
> Innate immune recognition of Mycobacterium tuberculosis and other pathogens
> Molecular mechanisms of macrophage functions
> Regulators of immune responses during infection and inflammation
> Discovery of novel anti-microbials