Research Network for Metals in Medicine

 

 

Dr Mary Collins

BSC (Hon), PhD, MRACI

Position: Lecturer in Pharmaceutical Chemistry

Affiliation: Faculty of Pharmacy, University of Sydney

Postal Address:
Faculty of Pharmacy
Pharmacy Building (A15)
University of Sydney
Sydney, NSW, 2006
AUSTRALIA

Phone: +61 (2) 9351 8584
Fax: +61 (2) 9351 4391
Email: maryc@pharm.usyd.edu.au
Webpage: http://www.pharm.usyd.edu.au/about/people/maryc.shtml


Research Profile

My research utilises the disciplines of medicinal chemistry, pharmacology, molecular biology and electrophysiology to investigate GABA receptors and transporters, and neuronal nicotinic acetylcholine (nACh) receptors. We study the interactions of small molecules with the receptor, develop structure-activity relationship (SAR) profiles, design and develop novel and selective drugs, and use complementary SAR studies by manipulating the receptor protein. These studies may lead to the development of drugs acting on the brain to treat neurological disorders such as epilepsy, schizophrenia, Parkinson's disease, anxiety, depression and Alzheimer's disease. Present research aims include:

  • To develop structure-activity relationship profiles of compounds (herbal and synthetic) that interact with neuronal nACh receptors, GABA receptors and GABA transporters
  • To study the effects of antipsychotics on recombinant GABA-A and GABA-C receptors in order to gain a better understanding of how these drugs aid schizophrenic patients.
  • To design and synthesise more potent and selective agents to probe the likely heterogeneity of neuronal nACh receptors, GABA receptors and GABA transporter.
  • To use site-directed mutagenesis and electrophysiological methods to identify key amino acid residues that may form part of the binding site and which may be involved in the assembly of the GABA receptors.
  • To use key agents to investigate modulatory sites on nACh receptors and GABA receptors by using single channel electrophysiology.
  • To determine the distribution of the most recently described GABA receptors, the GABA-C receptors, in the central nervous system (CNS).


Selected Publications

  1. Chebib M., Duke R.K., Allan R.A., Johnston G.A.R. (2001) The effects of cyclopentane and cyclopentene analogues of GABA at recombinant GABA-C receptors. European Journal of Pharmacology, in press
  2. Hanrahan J.R., Mewett K.N., Chebib M., Burden P.M. Johnston G.A.R. (2001) An improved, versatile synthesis of the GABA-C antagonists (1,2,5,6-tetrahydropyridin-4-yl)methyl phosphinic acid (TPMPA) and (piperidin-4-yl) methylphosphinic acid (P4MPA) J. Chem. Soc. Perkins Transactions I , 19, 2389-2392.
  3. Johnston GAR, Chebib M, Duke RK, (2000) 'Ionotropic GABA receptors: ligand gated ion channels' in Control and Diseases of Sodium Dependent Transport Proteins and Ion Channels, Edited by Y Suketa, Elsevier Science, Amsterdam, The Netherlands, p369 - 372
  4. Duke RK, Chebib M, Allan RD, Mewett KN, Johnston GAR (2000) (+)- and (-)- CAMP (cis-2-aminomethylcyclopropanecarboxylic acid), show opposite pharmacology at recombinant r1 and r2 GABAC receptors, Journal of Neurochemistry, 75 (6), 2602 - 2610
  5. Lieb I, Chebib M, Cooper B, Dias L, Balcar VJ (2000) Quantitative autoradiography of Na+-dependent [3H]L-aspartate binding to L-gluatamate transporters in rat brain: Structure-activitiy studies using L-trans-pyrrolidine-2,4-dicarboxylate (L-t-PDC) and 2-(carboxycyclopropyl)-glycine (CCG), Neurochemistry International, 36, 319-327.
  6. Chebib M, Johnston GAR, (2000) GABA activated ion channels: Medicinal chemistry and molecular biology, Perspective in Journal of Medicinal Chemistry, 43(8), 1427-1447
  7. Johnston GAR, Chebib M, Duke RK, Mewett KN, Mitrovic AD and Vandenberg RJ (1999) Medicinal chemistry and molecular pharmacology of GABA receptors and glutamate transporters complementary structure-activity relationships, Drug Development Research, 46, 255-260
  8. Chebib M, Johnston GAR, (1999) The ABC of GABA receptors: A brief review, Clinical and Experimental Pharmacology and Physiology, 26, 937-940
  9. Cordato DJ, Chebib M, Mather LE, Herkes GK, Johnston GAR (1999) Stereoselective interaction of thiopentone enantiomers with the GABAA receptor, British Journal of Pharmacology, 128, 77-82
  10. Chebib M, Mewett KN, Johnston GAR (1998) GABAC receptor antagonists differentiate between human r1 and r2 receptors expressed in Xenopus oocytes, European Journal of Pharmacology, 357, 227-234
  11. Duke RK, Allan RD, Chebib M, Greenwood JR, Johnston GAR (1998) Resolution and conformational analysis of diastereoisomers of cis- and trans-2-(aminomethyl)-1-carboxycyclopropanes, Tetrahedron Asymmetry, 9, 2533-2548
  12. Cooper B, Chebib M, Shen J, King NJC, Darvey IG, Kuchel PW, Rothstein JD, Balcar VJ (1998) Structural selectivity and molecular nature of L-glutamate transport in cultured human fibroblasts, Archives of Biochemistry and Biophysics, 353 (2), 356-364.
  13. Chebib M, Vandenberg RJ, Johnston GAR (1997) Analogues of g-aminobutyric acid (GABA) and trans-4-aminocrotonic acid (TACA) substituted in the 2 position as GABA - receptor antagonists, British Journal of Pharmacology, 122, 1551-1560.
  14. Chebib M, Vandenberg RJ, Froestl W, Johnston GAR (1997) Unsaturated phosphinic analogues of g-aminobutyric acid (GABA) as GABAC receptor antagonists, European Journal of Pharmacology, 329, 223-229
  15. Chebib M, Johnston GAR (1997) Stimulation of [3H]GABA and [3H]b-alanine release from rat brain slices by cis-4-aminocrotonic acid, Journal of Neurochemistry , 68, 786-794


Facilities

The Collins research team uses a multidisciplined approach and many different techniques are available/employed including:

  • Molecular biology
  • Electrophysiology
  • Cell culture
  • Radio-ligand binding
  • Neurochemistry
  • In situ hybridisation histochemistry
  • Immunohistochemistry
  • Autoradiography
  • Molecular modelling
  • Chemistry


International Linkages

Professor Rick Silverman (Northwestern University, USA)
Professor Povl Krogsgaard-Larsen (Royal Danish School of Pharmacy, Denmark)
Dr Wolfgang Froestl (Novartis, Switzerland)
Dr Bjarke Ebert (Royal Danish School of Pharmacy, Denmark)
Professor Susan Wonnacott (University of Bath, UK)
Professor Joachim Bormann (Ruhr University, Germany)