Dr Craig Clements - Researcher Profile

Craig Clements

Address

Department of Biochemistry & Molecular Biology
Faculty of Medicine, Nursing & Health Sciences, Clayton

Biography

New horizons in immunology

The pure science involved in studying the submicroscopic world of receptors on the body’s natural killer cells has occupied Dr Craig Clements’ attention for most of the past decade. But with a project in that field in its final stages, the ARC QEII Fellow is redirecting his expertise to the highly practical question of food security.

Craig specialises in using X-ray crystallography to determine the three-dimensional structure of proteins. He has been focused most recently on two families of receptors, the molecules found on a cell’s surface that pick up chemicaldetect signals from elsewhere within the organism.

Although their name might suggest otherwise, one of the roles of natural killer cells is to recognise healthy cells and protect them.

“It’s almost is a housekeeping function, just to keep ensure everything is healthy,” says Craig, who was awarded a grant under the Monash Research Accelerator program in 2010.

“I’ve been looking at the way these particular receptors on the natural killer cells can distinguish between a healthy cell and an infected or unhealthy cell.”

Work on one family, called killer-cell immunoglobulin-like receptors (or more simply KIR), is still under way., Bbut Craig has already achieved his research goals and published a paper on the other family, CD94/NKG2.

 “We were able to get the structure of one of the members of that family by itself and also in a complex with the other protein that it recognises,” he says.

The objects of Craig’s attention are so small that they cannot be studied as is. In order to determine their three-dimensional structure, researchers must turn them into crystals: several million protein molecules aligned in exactly the same orientation.

Achieving such crystals is a long and complex process but the result is something that researchers can X-ray to provide data for further analysis. 

“The idea of the crystal is a repeating lattice that essentially amplifies the scattering of the X-ray,” Craig says. “Each atom in the protein contributes to the scattering.”

His overall aim in this work is a greater fundamental understanding of immunological processes, through increasing our knowledge of the way cells recognise each other.
Although his findings are relevant to research into viruses, organ transplants, tissue rejection and cancer, he is not involved in generating therapies.

But as Craig looks to the future, he is considering projects with more immediately practical goals.

He sees a role for his skills in structural biology and X-ray crystallography in collaborative research looking at the plant world, with particular interest in biofortification -- improving the nutritional value of crops -- and increasing understanding of plants’ immune responses.

“I’ve come from an immunology background and I realised that the immune system of plants is poorly studied,” he says.

Two-fold plans include studying a bacterium that infects plants, causing major crop damage, and an investigation of the structure of rice enzymes, as part of a project aimed at increasing the grain’s iron content. Rice, though the staple food of billions of people, is very low in iron and dietary deficiencies can result.

 “I find it quite exciting that something I do could have some obvious practical application,” Craig says.

Qualifications

PhD, Biochemistry
Institution: University of Melbourne
Year awarded: 2001
BACHELOR OF SCIENCE(HONS)
Institution: University of Melbourne
Year awarded: 1995

Publications

Journal Articles

Zeng, L., Sullivan, L.C., Vivian, J.P., Walpole, N.G., Harpur, C.M., Rossjohn, J., Clements, C.S., Brooks, A.G., 2012, A structural basis for antigen presentation by the MHC class Ib molecule, Qa-1b, Journal Of Immunology [P], vol 188, issue 1, American Association of Immunologists, USA, pp. 302-310.

Vivian, J.P., Duncan, R.C., Berry, R., O'Connor, G.M., Reid, H.H., Beddoe, T.C., Gras, S., Saunders, P.M., Olshina, M.A., Widjaja, J.M., Harpur, C.M., Lin, J., Maloveste, S.M., Price, D.A., Lafont, B.A., McVicar, D.W., Clements, C.S., Brooks, A.G., Rossjohn, J., 2011, Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B, Nature [P], vol 479, issue 7373, Nature Publishing Group, UK, pp. 401-405.

Theodossis, A., Guillonneau, C., Welland, A.D., Ely, L.K., Clements, C.S., Williamson, N.A., Webb, A.I., Wilce, J.A., Mulder, R.J., Dunstone, M.A., Doherty, P.C., McCluskey, J., Purcell, A.W., Turner, S.J., Rossjohn, J., 2010, Constraints within major histocompatibility complex class I restricted peptides: presentation and consequences for T-cell recognition, Proceedings Of The National Academy Of Sciences Of The United States Of America [P], vol 107, issue 12, National Academy of Sciences, USA, pp. 5534-5539.

Burrows, S.R., Chen, Z., Archbold, J.K., Tynan, F.E., Beddoe, T.C., Kjer-Nielsen, L., Miles, J.J., Khanna, R., Moss, D.J., Liu, Y.C., Gras, S., Kostenko, L., Brennan, R.M., Clements, C.S., Brooks, A.G., Purcell, A.W., McCluskey, J., Rossjohn, J., 2010, Hard wiring of T cell receptor specificity for the major histocompatibility complex is underpinned by TCR adaptability, Proceedings Of The National Academy Of Sciences Of The United States Of America [P], vol 107, issue 23, National Academy of Sciences, USA, pp. 10608-10613.

Walpole, N.G., Kjer-Nielsen, L., Kostenko, L., McCluskey, J., Brooks, A.G., Rossjohn, J., Clements, C.S., 2010, The structure and stability of the monomorphic HLA-G are influenced by the nature of the bound peptide, Journal of Molecular Biology [P], vol 397, issue 2, Academic Press, UK, pp. 467-480.

Ebert, L.M., Liu, Y.C., Clements, C.S., Robson, N.C., Jackson, H.M., Markby, J.L., Dimopoulos, N., Tan, B.S., Luescher, I.F., Davis, I.D., Rossjohn, J., Cebon, J., Purcell, A.W., Chen, W., 2009, A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design, Cancer Research, vol 69, issue 3, American Association for Cancer Research, USA, pp. 1046-1054.

Beddoe, T.C., Chen, Z., Clements, C.S., Ely, L.K., Bushell, S.R., Vivian, J.P., Kjer-Nielsen, L., Pang, S.S., Dunstone, M.A., Liu, Y.C., Macdonald, W.A., Perugini, M.A., Wilce, M.C.J., Burrows, S.R., Purcell, A.W., Tiganis, T., Bottomley, S.P., McCluskey, J., Rossjohn, J., 2009, Antigen ligation triggers a conformational change within the constant domain of the alphabeta T cell receptor, Immunity [P], vol 30, issue 6, Cell Press, USA, pp. 777-788.

Archbold, J.K., Macdonald, W.A., Gras, S., Ely, L.K., Miles, J.J., Bell, M.J., Brennan, R.M., Beddoe, T.C., Wilce, M.C.J., Clements, C.S., Purcell, A.W., McCluskey, J., Burrows, S.R., Rossjohn, J., 2009, Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition, The Journal of Experimental Medicine, vol 206, issue 1, Rockefeller University Press, USA, pp. 209-219.

Macdonald, W.A., Chen, Z., Gras, S., Archbold, J.K., Tynan, F.E., Clements, C.S., Bharadwaj, M., Kjer-Nielsen, L., Saunders, P.M., Wilce, M.C.J., Crawford, F., Stadinsky, B., Jackson, D., Brooks, A., Purcell, A.W., Kappler, J., Burrows, S.R., Rossjohn, J., McCluskey, J., 2009, T cell allorecognition via molecular mimicry, Immunity [P], vol 31, issue 6, Cell Press, USA, pp. 897-908.

Gras, S., Burrows, S.R., Kjer-Nielsen, L., Clements, C.S., Liu, Y.C., Sullivan, L.C., Bell, M.J., Brooks, A.G., Purcell, A.W., McCluskey, J., Rossjohn, J., 2009, The shaping of T cell receptor recognition by self-tolerance, Immunity, vol 30, issue 2, Cell Press, USA, pp. 193-203.

Hopkins, E.J., Clements, C.S., Lin, J., Sullivan, L.C., Johnson, D., Huyton, T., Heroux, A., Hoare, H.L., Beddoe, T.C., Reid, H.H., Wilce, M.C., Brooks, A., Rossjohn, J., 2008, CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence, The Journal of Experimental Medicine, vol 205, issue 3, Rockefeller University Press, United States, pp. 725-735.

Hoare, H.L., Sullivan, L.C., Clements, C.S., Ely, L.K., Beddoe, T.C., Henderson, K., Lin, J., Reid, H.H., Brooks, A., Rossjohn, J., 2008, Subtle changes in peptide conformation profoundly affect recognition of the non-classical MHC class I molecule HLA-E by the CD94-NKG2 natural killer cell receptors, Journal of Molecular Biology, vol 377, issue 5, Academic Press, United Kingdom, pp. 1297-1303.

Sullivan, L.C., Clements, C.S., Rossjohn, J., Brooks, A., 2008, The major histocompatibility complex class Ib molecule HLA-E at the interface between innate and adaptive immunity, Tissue Antigens, vol 72, issue 5, Wiley-Blackwell Munksgaard, Denmark, pp. 415-424.

Clements, C.S., Kjer-Nielsen, L., McCluskey, J., Rossjohn, J., 2007, Structural studies on HLA-G: implications for ligand and receptor binding, Human Immunology, vol 68, issue 4, Elsevier Science Inc, New York NY USA, pp. 220-226.

Sullivan, L.C., Clements, C.S., Beddoe, T.C., Johnson, D., Hoare, H.L., Lin, J., Huyton, T., Hopkins, E.J., Reid, H.H., Wilce, M.C.J., Kabat, J., Borrego, F., Coligan, J.E., Rossjohn, J., Brooks, A., 2007, The heterodimeric assembly of the CD94-NKG2 receptor family and implications for human leukocyte antigen-E recognition, Immunity, vol 27, issue 6, Cell Press, Cambridge MA USA, pp. 900-911.

Kjer-Nielsen, L., Borg, N.A., Pellicci, D.G., Beddoe, T.C., 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/glycolipid recognition, Journal of Experimental Medicine, vol 203, issue 3, Rockefeller University Press, New York USA, pp. 661-673.

Ely, L.K., Beddoe, T.C., Clements, C.S., Matthews, J.M., Purcell, A.W., Kjer-Nielsen, L., McCluskey, J., Rossjohn, J., 2006, Disparate thermodynamics governing T cell receptor-MHC-1 interactions implicate extrinsic factors in guiding MHC restriction, Proceedings of the National Academy of Sciences of the United States of America, vol 103, issue 17, National Academy of Sciences, Washington USA, pp. 6641-6646.

Clements, C.S., Dunstone, M.A., Macdonald, W.A., McCluskey, J., Rossjohn, J., 2006, Specificity on a knife-edge: The alphabeta T cell receptor, Current Opinion in Structural Biology, vol 16, issue 6, Current Biology Ltd, London UK, pp. 787-795.

Hoare, H.L., Sullivan, L.C., Pietra, G., Clements, C.S., Lee, E.J., Ely, L.K., Beddoe, T.C., Falco, M., Kjer-Nielsen, L., Reid, H.H., McCluskey, J., Moretta, L., Rossjohn, J., Brooks, A.G., 2006, Structural basis for a major histocompatibility complex class Ib-restricted T cell response, Nature Immunology, vol 7, issue 3, Nature Publishing Group, New York USA, pp. 256-264.

Clements, C.S., Kjer-Nielsen, L., Kostenko, L., McCluskey, J., Rossjohn, J., 2006, The production, purification and crystallization of a soluble form of the nonclassical MHC HLA-G: the essential role of cobalt, Acta Crystallographica, vol 62, issue 1, Blackwell Publishing, Oxford England, pp. 70-73.

Ely, L.K., Green, K.J., Beddoe, T.C., Clements, C.S., Miles, J.J., Bottomley, S.P., Zernich, D., Kjer-Nielsen, L., Purcell, A.W., McCluskey, J., Rossjohn, J., Burrows, S.R., 2005, Antagonism of antiviral and allogeneic activity of a human public ctl clonotype by a single altered peptide ligand: Implications for allograft rejection, Journal of Immunology, vol 174, issue 9, American Association of Immunologists, Bethesda USA, pp. 5593-5601.

Clements, C.S., Kjer-Nielsen, L., Kostenko, L., Hoare, H.L., Dunstone, M.A., Moses, E.K., Freed, K., Brooks, A.G., Rossjohn, J., McCluskey, J., 2005, Crystal structure of HLA-G: A nonclassical MHC class I molecule expressed at the fetal-maternal interface, Proceedings of the National Academy of Sciences of the United States of America, vol 102, issue 9, National Academy of Sciences, Washington USA, pp. 3360-3365.

Tynan, F.E., Burrows, S.R., Buckle, A.M., Clements, C.S., Borg, N.A., Miles, J.J., Beddoe, T.C., Whisstock, J.C., Wilce, M.C.J., Silins, S.L., Burrows, J.M., Kjer-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, Nature Immunology, vol 6, issue 11, Nature Publishing Group, New York USA, pp. 1114-1122.

Borg, N.A., Ely, L.K., Beddoe, T.C., Macdonald, W.A., Reid, H.H., Clements, C.S., Purcell, A.W., Kjer-Nielsen, L., Miles, J.J., Burrows, S.R., McCluskey, J., Rossjohn, J., 2005, The CDR3 regions of an Immunodominant T cell receptor dictate the 'energetic landscape' of peptide-MHC recognition, Nature Immunology, vol 6, issue 2, Nature Publishing Group, New York USA, pp. 171-180.

Macdonald, W.A., Purcell, A.W., Mifsud, N.A., Ely, L.K., Williams, D.S., Chang, L., Gorman, J.J., Clements, C.S., Kjer-Nielsen, L., Koelle, D.M., Burrows, S.R., Tait, B.D., Holdsworth, R., Brooks, A.G., Lovrecz, G.O., Lu, L., Rossjohn, J., McCluskey, J., 2003, A naturally selected dimorphism within the HLA-B44 supertype alters Class I structure, peptide repertoire, and T cell recognition, Journal of Experiemental Medicine, vol 198, issue 5, Rockefeller University Press, New York USA, pp. 679-691.

Kjer-Nielsen, L., Clements, C.S., Purcell, A.W., Brooks, A.G., Whisstock, J.C., Burrows, S.R., McCluskey, J., Rossjohn, J., 2003, A structural basis for the selection of dominant T cell receptors in antiviral immunity, Immunity, vol 18, issue 1, Cell Press, Cambridge USA, pp. 53-64.

Clements, C.S., Reid, H.H., Beddoe, T.C., Tynan, F.E., Perugini, M., Johns, T.G., Bernard, C.C.A., Rossjohn, J., 2003, The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis, Proceedings of the National Academy of Sciences of the United States of America, vol 100, issue 19, National Academy of Sciences, Washington USA, pp. 11059-11064.

Kjer-Nielsen, L., Clements, C.S., Brooks, A.G., Purcell, A.W., McClusky, J., Rossjohn, J., 2002, The 1.5 Crystal Structure of a Highly Selected Antiviral T Cell Receptor Provides Evidence for a Structural Basis of Immonodominance, Structure, vol 10, issue 11, Cell Press, Cambridge MA USA, pp. 1521-1532.

Clements, C.S., Kjer-Nielsen, L., Macdonald, W.A., Brooks, A.G., Purcell, A.W., McClusky, J., Rossjohn, J., 2002, The production, purification and crystallization of a soluble heterdimeric form of a highly selected T-cell receptor in its unliganded and liganded state, Acta Crystallography, vol 58, issue 12, Blackwell Munksgaard, Copenhagen Denmark, pp. 2131-2134.

Kjer-Nielsen, L., Clements, C.S., Brooks, A.G., Purcell, A.W., Fontes, M.R., McCluskey, J., Rossjohn, J., 2002, The structure of HLA-B8 complexed to an immunodominant viral determinant: peptide-induced conformational changes and a mode of MHC class 1 dimerisation1, Journal of Immunology, vol 169, issue 9, American Association of Immunologists, Bethesda MD USA, pp. 5153-5160.

Conference Proceedings

Kjer-Nielsen, L., Beddoe, T.C., Kostenko, L., Clements, C.S., Williamson, N.A., Besra, G.S., Reid, H.H., Bharadwaj, M., Godfrey, D.I., McCluskey, J., Rossjohn, J., 2005, A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1D-mediated antigen recognition, Tissue Antigens, 29 November 2005 - 3rd December 2005, Blackwell Publishing, Oxford England, p. 365.

Tynan, F.E., Burrows, S.R., Buckle, A.M., Clements, C.S., Borg, N., Beddoe, T.C., Whisstock, J.C., Wilce, M.C.J., Silins, S.L., Burrows, J.M., Kjer-Nielsen, L., Kostenko, L., Purcell, A.W., McCluskey, J., Rossjohn, J., 2005, A super-bulged epitope and single amino acid polymorphism identify critical features for T cell recognition, Tissue Antigens, 29 November 2005 - 3rd December 2005, Blackwell Publishing, Oxford England, p. 571.

Hoare, H.L., Sullivan, L.C., Pietra, G., Clements, C.S., Beddoe, T.C., Kjer-Nielsen, L., Reid, H.H., McCluskey, J., Moretta, L., Rossjohn, J., 2005, Recognition of the non-classical MHC class I molecule, HLA-E, by the adaptive immune system, Tissue Antigens, 29 November 2005 - 3rd December 2005, Blackwell Publishing, Oxford England, p. 443.

Postgraduate Research Supervisions

Completed Supervision

Student:
Walpole, N.
Program of Study:
Structural investigation of human class Ib Major Histocompatibility Complex molecules in innate and adaptive immunity. (PHD) 2012.
Supervisors:
Clements, C (Joint), Rossjohn, J (Joint-Co).