Borg Lab research
About Dr Natalie Borg
Natalie obtained her Ph.D from the University of Melbourne, Department of Microbiology and Immunology in 2003. Following this she was a post-doc at the Department of Biochemistry and Molecular Biology at Monash University, and now pursues her own research vision as a laboratory head within the same department. Natalie has received prestigious fellowships including an NHMRC Peter Doherty fellowship, an NHMRC Career Development Award, a L'Oreal for Women in Science Fellowship and an ARC Future Fellowship.
Our laboratory is focused on understanding how we defend ourselves against microbial pathogens, and on the flip-side, how microbial pathogens block or exploit host immunity for their survival. We initially identify new host-pathogen and host-host protein interactions using a proteomics approach. We explore the significance of these novel interactions using a structural/functional approach that marries cell-based assays with structural/biochemical/biophysical tools. This knowledge helps us to understand how proteins in our innate immune system work and how they are hijacked by microbial proteins to benefit infection. Pathogens of interest include influenza, respiratory syncytial virus, dengue virus, West Nile virus and members of the Enterobacteriaceae (eg. Salmonella, Shigella).
In an era when infectious disease remains a significant global challenge due to a lack of treatment options or emerging drug resistance we urgently need to devise new strategies to combat microbial infections. Our academic research often highlights opportunities to translate our research and we are currently developing broad-spectrum viral inhibitors that also have application for cancer therapy.
Read about the drug development funding from BioCurate that we received for our project - A new target for both viral infection and cancer.
1. Decoding innate anti-viral immunity
Viral infection is a significant cause of global mortality and economic burden. Did you know the Spanish influenza outbreak of 1918 killed more than 40 million people? Or that hepatitis B is the most common infectious disease in the world, causing 600,000 deaths each year?
Host organisms detect and clear viral infection by coordinating between the innate and adaptive arms of immunity. The retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are antiviral pattern recognition receptors that act as sentinels for viral RNA from pathogens of significance to human health such as influenza, hepatitis B, hepatitis C and respiratory syncytial virus. Once activated these innate immune RLR receptors recruit downstream signalling proteins that lead to the induction of type I interferons (IFN) such as IFN-a and IFN-b. These type I IFNs activate JAK-STAT (Janus kinase/signal transducers and activators of transcription) signalling, leading to the induction of hundreds of genes that control the viral infection. We are interested in identifying new connections between proteins in the RLR signalling cascade and the functional relevance of the interactions. Our current focus is how E3 ligases posttranslational modify RLR signalling proteins with ubiquitin to modulate signalling.
2. Microbial manipulation of innate immunity
The success of a pathogen is partly determined by how well it can utilise host cell proteins for replication and also evade the host innate immune response. Well-known RNA viruses like influenza A and hepatitis C implement immune evasion strategies. Unfortunately, these immune evasion mechanisms are often poorly understood and hampered by our limited understanding of how antiviral immunity is activated by innate immune receptors such RIG-I. We are interested in mechanistically understanding how microbial pathogens target host cell proteins within the RLR signalling cascade.
3. Nuclear trafficking of host and microbial proteins
The correct subcellular localisation of host and microbial proteins is central to their function. We are interested in better understanding how host and microbial proteins use nuclear transport receptors to shuttle between the nucleus and cytoplasm. Agents that selectively alter the nuclear transport of host or microbial proteins have potential application as therapeutics for microbial pathogens of significance.
Visit Dr Borg’s Monash research profile to see a full listing of current projects.
We use a holistic approach to study our innate immune response to infection. Techniques used within the laboratory include molecular biology, recombinant protein expression, protein purification, X-ray crystallography, small angle X-ray scattering, analytical ultracentrifugation, biochemical assays, high-resolution imaging, gene knockdown/knockouts, luciferase assays, coimmunoprecipitation.
We collaborate with many scientists and research organisations around the world. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).
Student research projects
The Borg Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.
Please visit Supervisor Connect to explore the projects currently available in our Lab.