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Dr Natalie Borg

NHMRC Career Development Fellow

natalie borg

 

Tel:     +61 3 990 51429

Fax:    +61 3 990 53726

Office: Room 108, Building 13C

Email:  natalie.borg@med.monash.edu.au

Research Group Members:

Luke Cossins (Research Assistant)

 

Proteins are an essential component of all living organisms and hence must function correctly to prevent disease.  As the function of a protein is directly related to its shape, the Borg laboratory uses a combined functional/structural approach to understand the function, biology and structure of proteins important in human health.  These include proteins involved in the human immune response, neural development and cancer.

Techniques used within the laboratory include molecular biology, recombinant protein expression using insect and bacterial cells, protein purification using a Fast Protein Liquid Chromatography system, X-ray crystallography, protein-protein interaction analysis eg. surface plasmon resonance, tissue culture and relevant cellular assays.

Research Projects

Anti-viral immunity

(in collaboration with Dr Ashley Mansell, Monash Institute of Medical Research)

Our immune system has two immediate defence strategies to detect a viral infection and mount an anti-viral immune response.  One of these strategies involves the RIG-like helicase (RLH) family of protein receptors, which includes the retinoic acid inducible gene-I (RIG-I) cytosolic receptor.  This receptor recognizes intracellular double stranded RNA from viruses such as hepatitis C and measles and initiates an anti-viral response via the activation of NF-Kappa Beta and the production of type I interferons.  It is known that a complex network of signaling molecules regulate the RLH signaling cascade.  This research involves the investigation of a key player involved in regulating the RLH signaling cascade.

Development

(In collaboration with Professor James Whisstock & Assoc. Prof. Phillip Bird, Monash University)

There are three members in the BMP/RA-Inducible Neural-specific Protein (BRINP) family including BRINP1, BRINP2 and BRINP3.  The BRINP genes are expressed in neuronal cells in the central and peripheral nervous system from early embryonic stages to adulthood.  Here they are believed to be key players in neural cell function and development.  BRINP1 is also a candidate tumour suppressor gene for bladder cancer.

Members of the BRINP family of proteins have been highly conserved during evolution, indicating an evolutionarily important role.  Yet, BRINP family members have no sequence homology with known protein domains besides the MACPF superfamily.  Members of the MACPF superfamily play key roles in vertebrate immunity, neural cell migration and embryonic development. The aim of this research is to evaluate the function and structure of the BRINP family members in order to gain an understanding of their physiological role.

Cancer

(in collaboration with Dr Greg Hannigan, Monash Institute of Medical Research)

Integrin-linked kinase (ILK) is an adaptor and a kinase that is implicated in the regulation of processes that can lead to cancer development.  Various cancers have enhanced ILK expression, including cancer of the prostate, colon, breast and ovaries.  It has been shown that small-molecule ILK inhibitors that reduce the expression or activity of ILK can inhibit tumour growth.  For these reasons ILK is a potential target for cancer therapeutics.  The aim of this research is to develop our understanding of the structure and function of ILK, including how ILK interacts with its substrates.

Opportunities in the Borg Lab

Potential honours and PhD students are welcome to drop by and chat at any time.

Links

L'Oréal Australia For Women in Science Award

Natalie Borg's Publications

  • Borg, N.A*., Wun, K.S*., Kjer-Nielsen, L., Beddoe, T., Koh, R., Richardson, S.K., Thakur, M., Howell, A.R., Scott-Browne, J.P., Gapin, L., Godfrey, D.I., McCluskey, J., Rossjohn, J. (2008). A minimal binding footprint on CD1d-glycolipid is a basis for selection of the unique human NKT TCR. J. Exp Med. 205(4), 939-949.
  • Henderson, K.., Reid, H.H., Borg, N.A., Broughton, S.E., Huyton, T., Anderson, R.P., McCluskey, J., Rossjohn, J.  (2007). The production and crystallization of the human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 complexed with deamidated gliadin peptides implicated in Coeliac disease.  Acta Crystallogr Sect F Struct Biol Cryst Commun. 63 (Pt 12), 1021-1025.
  • Scott-Browne, J.P., Matsuda, J.L., Mallevaey, T., White, J., Borg, N.A., McCluskey, J., Rossjohn, J., Kappler, J., Marrack, P., Gapin, L.  (2007). Germline encoded recognition of diverse glycolipids by NKT cells. Nat Immunol. 8(10), 1105-1113.
  • Henderson, K.N., Tye-Din, J.A., Reid, H.H., Chen, Z., Borg, N.A., Beissbarth, T., Tantham, A., Mannering, S.I., Purcell, A.W., Dudek, N.L., van Heel, D.A., McCluskey, J., Rossjohn, J., Anderson, RP. (2007) A structural and immunological basis for the role of human leukocyte antigen DQ8 in Coeliac Disease. Immunity. 27(1), 23-24.
  • Borg, N.A., Wun, K.S., Kjer-Nielsen, L., Wilce, M.C.J., Pellici, D.G., Koh, R., Besra, G.S., Bharadwaj, M., Godfrey, D.I., McCluskey, J., Rossjohn, J.  (2007).  CD1d-lipid antigen recognition by the semi-invariant NKT cell receptor.  Nature. 448 (7149), 44-49.
  • Tynan, F.E*., Reid, H.H*, Kjer-Nielsen, L., Miles, JJ., Wilce, M.C.J., Kostenko, L., Borg, N.A., Williamson, N.A., Purcell, A.W., Burrows, S.R., McCluskey, J., Rossjohn, J.  (2007). A T cell receptor flattens a bulged antigenic peptide presented by a major histocompatibility class I molecule.  Nat Immunol. 8 (3), 268-276.
  • Borg, N.A*., Miles, J.J*., Brennan, R.M., Tynan, F.E., Nielsen, K., Silins, S.L., Bell, M.J., Burrows, J.M., McCluskey, J., Rossjohn, J., Burrows, S.R.  (2006). TCRa genes direct MHC-restriction in the potent human T cell response to a highly mobile class-I-bound epitope. J. Immunol. 177 (10), 6804-6814.
  • Borg, N.A*., Kjer-Nielsen, L*., Pellicci, D.G., Beddoe, T., Kostenko, L., Clements, C.S., Williamson, N.A., Smyth, M.J.,  Besra, G.S., Reid, H.H., Bharadwaj, M., Godfrey, D.I., Rossjohn, J., McCluskey, J. (2006). A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d-mediated antigen recognition.  J. Exp. Med. 203 (3), 661-673.
  • Tynan, F.E*., El-Hassen, D*., Purcell, A.W., Burrows, J., Borg, N.A., Miles, J.J., Williamson, N.A., Green, K.J., Tellam, J., Kjer-Nielsen, L., McCluskey, J., Rossjohn, J., Burrows, S.R.  (2005). The immunogenicity of a viral cytotoxic T cell epitope is controlled by its MHC-bound conformation. J. Exp. Med. 202 (9), 1249-1260.
  • Tynan, F.E*., Burrows, S.R*., Buckle, A.M*., Clements, C.S., Borg, N.A., Miles, J.J., Beddoe, T., Whisstock, J.C., Wilce, M.W., Silins, S.L., Burrows, J.M., Nielsen, L., Kostenko, L., Purcell, A.W., McCluskey, J., Rossjohn, J.  (2005). T cell receptor recognition of a ‘super-bulged’ major histocompatibility complex class I-bound peptide.  Nat. Immunol. 6 (11), 1114-1122.
  • Miles, J.J*., Elhassen, D*., Borg, N.A., Silins, S., Tynan, F.E., Burrows, J.M., Purcell, A.W., Kjer-Nielsen, L., Rossjohn, J., Burrows, S.R., McCluskey, J.  (2005) CTL recognition of a bulged viral peptide involves biased TCR selection.  J. Immunol. 175 (6), 3826-3834. 
  • Borg, N.A*., Tynan, F.E*., Miles, J.J., Beddoe, T., El-Hassen, D., Silins, S.L., van Zuylen, W.J., Purcell, A.W., Kjer-Nielsen, L., McCluskey, J., Burrows, S.R., Rossjohn, J.  (2005). High resolution structures of highly bulged viral epitopes bound to major histocompatability complex class I. Implications for T-cell receptor engagement and T-cell immunodominance. J. Biol. Chem. 280 (25), 23900-23909.
  • Borg, N.A*., Ely, L.K*., Beddoe, T., MacDonald, W.A., Reid, H.H., Clements, C.S., Purcell, A.W., Kjer-Nielsen, L., Miles, J.J., Burrows, S.R., McCluskey, J. and Rossjohn, J. (2005).  The CDR3 regions of an immunodominant ab T cell receptor dictate the ‘energetic landscape’ of peptide-MHC recognition.  Nat. Immunol. 6 (2), 171-180.
  • Borg N.A*., Webb A.I*., Dunstone M.A., Kjer-Nielsen, L., Beddoe, T., McCluskey, J., Carbone, F.R., Bottomley, S.P., Aguilar, M.I., Purcell, A.W., Rossjohn, J. (2004). The structure of H-2K(b) and K(bm8) complexed to a herpes simplex virus determinant: evidence for a conformational switch that governs T cell repertoire selection and viral resistance. J. Immunol. 173 (1), 402-409.
  • Borg, N.A*., Lawrence, M.C*., Streltsov, V.A., Pilling, PA., Epa, V.C., Varghese, J.N., McKimm-Breschkin J.L., Colman P.M. (2004). Structure of the haemagglutinin-neuraminidase from human parainfluenza virus type III.  J. Mol. Biol. 335 (5), 1343-1357.

          Book Chapters

  • Borg, N.A., Kjer-Nielsen, L., McCluskey, J., Rossjohn, J. A structurally sound insight into natural killer T cell receptor recognition of CD1d. In Advances in Experimental Medicine and Biology, Vol. 598. Chapter 3.  Lambris, J.D. (Ed.).  2007, XVI, 438 p.98.

 

 

  
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