Dr John Bruning

John Bruning
Senior Lecturer
School of Biological Sciences
Faculty of Sciences

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Dr John Bruning

I head the Laboratory of Protein Crystallography which studeis Nuclear Receptors, Microbial Enzymology, and Broad-Based Cancer Therapeutics. Understanding human disease requires knowledge of the structure-function relationships in protein sensor modulation.This knowledge is incomplete on a broad spectrum of biological systems including nuclear receptor (NR) signalling, proteins involved in cancer biology, and pathogen protein machinery. Our research is focused on understanding these classes of protein interactions on an atomic level. In addition to gaining a basic understanding of protein mechanism, we also focus on structure guided drug design. In our work in understanding NR signalling, we have uncovered new paradigms in NR allostery. These allosteric modulations can now be further studied on a broader scale and harnessed to employ structure guided drug design. Work in the tuberculosis (TB) structural biology consortium has led to a quantum leap in understanding enzymology of the pathogen allowing for new chemotherapy development. We wish to use similar methodology to study a fungal pathogen for the discovery of new anti-fungal molecules.Our research with proteins of the human replication fork, such as PCNA (Proliferating Cellular Nuclear Antigen) has uncovered atomic determinants of these protein modulators that can be used as new paradigms for cancer therapeutic targeting. We will continue this research to aid in the discovery of alternative cancer therapeutic targets and seek to understand their structure-function relationship.

Appointments

Date Position Institution name
2016 Adjunct Professor The Scripps Research Institute
2016 Senior Lecturer Level C (Tenured) The University of Adelaide
2012 - 2015 Lecturer Level B The University of Adelaide
2007 - 2012 Associate Research Scientist Texas A&M University
2005 - 2007 Post-doctoral Research Associate Scripps Research Institute

Education

Date Institution name Country Title
1998 - 2004 Rice University United States PhD
1994 - 1997 Texas A&M University USA BSc

Postgraduate Training

Date Title Institution Country
2007 - 2012 Assistant Research Scientist Texas A&M USA
2005 - 2007 Post-doctoral Research Assistant The Scripps Research Institute USA

Journals

Year Citation
2017 Stevens, T., Song, S., Bruning, J., Choo, A. & Baxter, S. (2017). Expressing a moth abcc2 gene in transgenic Drosophila causes susceptibility to Bt Cry1Ac without requiring a cadherin-like protein receptor. Insect Biochemistry and Molecular Biology, 80, 61-70. 10.1016/j.ibmb.2016.11.008
2017 Rajapaksha, H., Bhatia, H., Wegener, K., Petrovsky, N. & Bruning, J. (2017). X-ray crystal structure of rivoglitazone bound to PPARγ and PPAR subtype selectivity of TZDs. Biochimica et Biophysica Acta - General Subjects, 1861, 8, 1981-1991. 10.1016/j.bbagen.2017.05.008
2017 Frkic, R., He, Y., Rodriguez, B., Chang, M., Kuruvilla, D., Ciesla, A. ... Bruning, J. (2017). Structure-Activity Relationship of 2,4-Dichloro-N-(3,5-dichloro-4-(quinolin-3-yloxy)phenyl)benzenesulfonamide (INT131) Analogs for PPARγ-Targeted Antidiabetics. Journal of Medicinal Chemistry, 60, 11, 4584-4593. 10.1021/acs.jmedchem.6b01727
2017 Sternicki, L., Wegener, K., Bruning, J., Booker, G. & Polyak, S. (2017). Mechanisms governing precise protein biotinylation. Trends in Biochemical Sciences, 42, 5, 383-394. 10.1016/j.tibs.2017.02.001
2017 Marshall, A., Kroker, A., Murray, L., Gronthos, K., Rajapaksha, H., Wegener, K. & Bruning, J. (2017). Structure of the sliding clamp from the fungal pathogen Aspergillus fumigatus (AfumPCNA) and interactions with Human p21. FEBS Journal, 284, 6, 985-1002. 10.1111/febs.14035
2016 Zhang, X., Bruning, J., George, J. & Abell, A. (2016). A mechanistic study on the inhibition of α-chymotrypsin by a macrocyclic peptidomimetic aldehyde. Organic and Biomolecular Chemistry, 14, 29, 6970-6978. 10.1039/c6ob01159d
2016 Van Marrewijk, L., Polyak, S., Hijnen, M., Kuruvilla, D., Chang, M., Shin, Y. ... Bruning, J. (2016). SR2067 reveals a unique kinetic and structural signature for PPARγ partial agonism. ACS Chemical Biology, 11, 1, 273-283. 10.1021/acschembio.5b00580
2016 Stechschulte, L., Czernik, P., Rotter, Z., Tausif, F., Corzo, C., Marciano, D. ... Lecka-Czernik, B. (2016). PPARG Post-translational modifications regulate bone formation and bone resorption. EBioMedicine, 10, 174-184. 10.1016/j.ebiom.2016.06.040
2015 Kroker, A. & Bruning, J. (2015). p21 exploits residue Tyr151 as a tether for high-affinity PCNA binding. Biochemistry, 54, 22, 3483-3493. 10.1021/acs.biochem.5b00241
2015 Coleman, T., Chao, R., Bruning, J., De Voss, J. & Bell, S. (2015). CYP199A4 catalyses the efficient demethylation and demethenylation of para-substituted benzoic acid derivatives. RSC Advances, 5, 64, 52007-52018. 10.1039/c5ra08730a
2015 Jia, Y., Wong, D., Sweetman, C., Bruning, J. & Ford, C. (2015). New insights into the evolutionary history of plant sorbitol dehydrogenase. BMC Plant Biology, 15, 1, 101-1-101-23. 10.1186/s12870-015-0478-5
2015 Marciano, D., Kuruvilla, D., Boregowda, S., Asteian, A., Hughes, T., Garcia-Ordonez, R. ... Griffin, P. (2015). Pharmacological repression of PPARγ promotes osteogenesis. Nature Communications, 6, 7443-1-7443-7. 10.1038/ncomms8443
2015 Kojetin, D., Matta-Camacho, E., Hughes, T., Srinivasan, S., Nwachukwu, J., Cavett, V. ... Nettles, K. (2015). Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. Nature Communications, 6, 8013-1-8013-14. 10.1038/ncomms9013
2015 Kroker, A. & Bruning, J. (2015). Review of the structural and dynamic mechanisms of PPAR γ partial agonism. PPAR Research, 2015, 816856-1-816856-15. 10.1155/2015/816856
2014 Sullivan, A., Raimondo, A., Schwab, T., Bruning, J., Froguel, P., Farooqi, I. ... Whitelaw, M. (2014). Characterization of human variants in obesity-related SIM1 protein identifies a hot-spot for dimerization with the partner protein ARNT2. Biochemical Journal, 461, 3, 403-412. 10.1042/BJ20131618
2014 Chua, K., Pietsch, M., Zhang, X., Hautmann, S., Chan, H., Bruning, J. ... Abell, A. (2014). Macrocyclic protease inhibitors with reduced peptide character. Angewandte Chemie International Edition, 53, 30, 7828-7831. 10.1002/anie.201404301
2014 Reddy, M., Breda, A., Bruning, J., Sherekar, M., Valluru, S., Thurman, C. ... Sacchettini, J. (2014). Structure, activity, and inhibition of the carboxyltransferase β-Subunit of acetyl coenzyme a carboxylase (AccD6) from mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy, 58, 10, 6122-6132. 10.1128/AAC.02574-13
2014 Bersten, D., Bruning, J., Peet, D. & Whitelaw, M. (2014). Human variants in the Neuronal Basic Helix-Loop-Helix/ Per-Arnt-Sim (bHLH/PAS) transcription factor complex NPAS4/ARNT2 disrupt function. M. Katoh (Ed.). PLoS One, 9, 1, e85768-1-e85768-11. 10.1371/journal.pone.0085768
2013 Ramachandrappa, S., Raimondo, A., Cali, A., Keogh, J., Henning, E., Saeed, S. ... Farooqi, I. (2013). Erratum: Rare variants in single-minded 1 (SIM1) are associated with severe obesity (Journal of Clinical Investigation (2013) 123:7 (3042-3050) DOI: 10.1172/JCI68016). Journal of Clinical Investigation, 123, 8, 3635-. 10.1172/JCI72103
2013 Bonnefond, A., Raimondo, A., Stutzmann, F., Ghoussaini, M., Ramachandrappa, S., Bersten, D. ... Froguel, P. (2013). Loss-of-function mutations in SIM1 contribute to obesity and Prader-Willi-like features. Journal of Clinical Investigation, 123, 7, 3037-3041. 10.1172/JCI68035
2013 Ramachandrappa, S., Raimondo, A., Cali, A., Keogh, J., Henning, E., Saeed, S. ... Farooqi, I. (2013). Rare variants in single-minded 1 (SIM1) are associated with severe obesity. Journal of Clinical Investigation, 123, 7, 3042-3050. 10.1172/JCI68016
2013 Mosser, R., Reddy, M., Bruning, J., Sacchettini, J. & Reinhart, G. (2013). Redefining the role of the quaternary shift in bacillus stearothermophilus phosphofructokinase. Biochemistry, 52, 32, 5421-5429. 10.1021/bi4002503
2012 Mosser, R., Reddy, M., Bruning, J., Sacchettini, J. & Reinhart, G. (2012). Structure of the apo form of Bacillus Stearothermophilus Phosphofructokinase. Biochemistry, 51, 3, 769-775. 10.1021/bi201548p
2011 Zhang, J., Chalmers, M., Stayrook, K., Burris, L., Wang, Y., Busby, S. ... Griffin, P. (2011). DNA binding alters coactivator interaction surfaces of the intact VDR-RXR complex. Nature Structural and Molecular Biology, 18, 5, 556-563. 10.1038/nsmb.2046
2011 Chim, N., Habel, J., Johnston, J., Krieger, I., Miallau, L., Sankaranarayanan, R. ... Goulding, C. (2011). The TB structural genomics consortium: a decade of progress. Tuberculosis, 91, 2, 155-172. 10.1016/j.tube.2010.11.009
2011 Bruning, J., Murillo, A., Chacon, O., Barletta, R. & Sacchettini, J. (2011). Structure of the Mycobacterium tuberculosis D-alanine:D-alanine Ligase, a target of the antituberculosis drug D-Cycloserine. Antimicrobial Agents and Chemotherapy, 55, 1, 291-301. 10.1128/AAC.00558-10
2011 Choi, J., Banks, A., Kamenecka, T., Busby, S., Chalmers, M., Kumar, N. ... Griffin, P. (2011). Anti-diabetic actions of a non-agonist PPARgamma ligand that blocks Cdk5-mediated phosphorylation. Nature, 477, 7365, 477-481. 10.1038/nature10383
2010 Bruning, J., Parent, A., Gil, G., Zhao, M., Nowak, J., Pace, M. ... Nettles, K. (2010). Coupling of receptor conformation and ligand orientation determine graded activity. Nature Chemical Biology, 6, 11, 837-843. 10.1038/nchembio.451
2009 Reddy, M., Palaninathan, S., Bruning, J., Thurman, C., Smith, D. & Sacchettini, J. (2009). Structural insights into the mechanism of the allosteric transitions of Mycobacterium Tuberculosis cAMP receptor protein. Journal of Biological Chemistry, 284, 52, 36581-36591. 10.1074/jbc.M109.041343
2008 Dai, S., Chalmers, M., Bruning, J., Bramlett, K., Osborne, H., Montrose-Rafizadeh, C. ... Griffin, P. (2008). Prediction of the tissue-specificity of selective estrogen receptor modulators by using a single biochemical method. Proceedings of the National Academy of Sciences of the United States of America, 105, 20, 7171-7176. 10.1073/pnas.0710802105
2008 Nettles, K., Bruning, J., Gil, G., Nowak, J., Sharma, S., Hahm, J. ... Greene, G. (2008). NFκB selectivity of estrogen receptor ligands revealed by comparative crystallographic analyses. Nature Chemical Biology, 4, 4, 241-247. 10.1038/nchembio.76
2007 Bruning, J., Chalmers, M., Prasad, S., Busby, S., Kamenecka, T., He, Y. ... Griffin, P. (2007). Partial agonists activate PPARγ using a helix 12 independent mechanism. Structure, 15, 10, 1258-1271. 10.1016/j.str.2007.07.014
2007 Nettles, K., Bruning, J., Gil, G., O'Neill, E., Nowak, J., Hughs, A. ... Greene, G. (2007). Structural plasticity in the oestrogen receptor ligand-binding domain. EMBO Reports, 8, 6, 563-568. 10.1038/sj.embor.7400963
2007 Zhou, H., Nettles, K., Bruning, J., Kim, Y., Joachimiak, A., Sharma, S. ... Katzenellenbogen, J. (2007). Elemental isomerism: a boron-nitrogen surrogate for a carbon-carbon double bond increases the chemical diversity of estrogen receptor ligands. Chemistry & Biology, 14, 6, 659-669. 10.1016/j.chembiol.2007.04.009
2004 Bruning, J. & Shamoo, Y. (2004). Structural and thermodynamic analysis of human PCNA with peptides derived from DNA polymerase-δ p66 subunit and flap endonuclease-1. Structure, 12, 12, 2209-2219. 10.1016/j.str.2004.09.018

Conference Papers

Year Citation
2010 Mosser, R., Reddy, M., Bruning, J., Sacchettini, J. C. & Reinhart, G. D. (2010). Redefining the Role of the Quaternary Shift in the Allosteric Inhibition of Bacillus Stearothermophilus Phosphofructokinase.
2007 Chalmers, M. J., Busby, S. A., Prasad, S., Bruning, J. B., Pascal, B. D., Southern, M. R. & Griffin, P. R. (2007). P97-S A High-Throughput Method for the characterization of Nuclear Receptor Dynamics. ABRF '07: Creating the Biological Roadmap. Tampa Florida.
  • ARC LIEF Grant (2014). LE15010023.  Michael, Dr. Micahel Z; Booker, A/Prof., Grant W; Venter, Dr. Henrietta; Pitson, Prof. Stuart M; McKinnon, Prof. Ross A; Abell, Prof. Andrew D; Soole, A/Prof. Kathleen L; Sykes, Prof. Pamela J; Bruning, Dr. John B. “High Throughput Screening Facility.” ($860,000).
  • Environment Institute Major Collaborative Project (2015). Dr. Frank Reith, Prof. Peter Hoffmann, Dr. Florian Weiland, Dr. Benjamin Wade, Dr. John Bruning. ($50,000).
  • Biochemistry Discipline Collaborative Research Grant (2015-2018).  Bruning, JB and Booker, GW.  “Structural studies of Aspergillus fumigatus enzyme targets for drug discovery.” ($45,000).
  • AIB Labs, Research Infrastructure Fund (2015).  Parkinson-Lawrence, E., Polyak, S.W., Brooks, D., Booker, G.W., Forbes, B.E., Pitson, S., Cowin, A., Bruning, J., Butler, L. ($12,793).
  • IPAS Pilot Projects (2015).  Krogsgaard-Larsen, N.; Bruning, J.B.; Luiten, A.; Callen, D.; Zhang, X.Z.; Alaknanda, A.  “First Steps toward a Cancer Biosensor.” ($6,000).
  • Australian Synchrotron CAP (2013). CAP6919. Hrmova, M. and Bruning, J.B.  “X-ray crystal structures of plant and mammalian proteins, and protein design.”
  • Australian Synchrotron CAP (2014). CAP8221. Hrmova, M. and Bruning, J.B.  “X-ray crystal structures of plant and mammalian proteins, and protein design.”
  • BIOCHEM3000 – Molecular and Structural Biology
  • BIOCHEM3230 – Molecular and Structural Biology (Biomedical Science)
  • BIOCHEM3125 – Advanced Molecular Biology IIIA (Biochemistry)
  • BIOCHEM3001 – Cancer, Stem Cells and Development III
  • BIOCHEM3235 – Cancer, Stem Cells and Development III (Biomedical Science)
  • BIOCHEM3520 – Cancer, Stem Cells and Development (Theory) III
  • BIOCHEM3225 – Advanced Molecular Biology IIIB (Biochemistry)
  • BIOCHEM2500 – Biochemistry II: Molecular & Cell Biology
  • BIOCHEM2502 – Biochemistry II (Biotech): Molecular & Cell Biology
  • BIOCHEM2504 – Biochemistry II (Mol Biol):  Molecular & Cell Biology
  • BIOLOGY1201 – Biology I – Human Perspectives
  • CHEMENG 2015 - Principles of Biotechnology II
  • BIOTECH7000 – Advanced Research Platforms
  • BIOTECH7001 – Drug Discovery and Development
  • Science2300 – Principles and Practice of Research

 

Completed Higher Degree Supervission:

  • Alice Kroker, Honours 2013
  • Ben Keiller, Honours, 2014
  • Long Tan, Masters 2014
  • Yong Jia, PhD 2016
  • Rebecca Frkic, Honours 2016

Current Higher Degree Students:

  • Rebecca Frkic, PhD
  • Alice Kroker, Masters
  • Andrew Marshall, PhD
  • Jia Truong, PhD
  • Roman Lenchine, PhD
  • Jordan Vihermaki, Honours
  • Lawrence Beltrame, Honours
  • Ibrahim Saidi, Masters
  • Emi Schutz, Masters
Position
Senior Lecturer
Phone
83135218
Fax
8313 4362
Campus
North Terrace
Building
Molecular Life Sciences
Room Number
2 43
Org Unit
Molecular and Cellular Biology

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