Professor Andrew Tobin

Professor of Molecular Pharmacology (Institute of Molecular Cell & Systems Biology)

telephone: 01413308494
email: Andrew.Tobin@glasgow.ac.uk

ORCID iD https://orcid.org/0000-0002-1807-3123

Biography

Andrew attended Queen Mary College, University of London where he attained a 1st class honours degree in Biochemistry. Following D.Phil studies at the University of Oxford under the supervision of Dr. Neville Osborne at the Nuffield Laboratory of Ophthalmology Andrew spent two years at Bristol Myers, Squibb in Princeton, New Jersey working with Mariano Barbacid on oncogene discovery. Returning to the UK in 1991 as a post doctoral fellow at the University of Leicester with Stefan Nahorski allowed Andrew to research mechanisms of regulation of G protein coupled receptors (GPCRs). He establish an independent group in 1996 with the first of three Wellcome Trust Senior Research Fellowships (SRF). Primarily focused on the physiological function and modes of drug action at GPCRs, Andrew’s group have investigated key novel paradigms in GPCR biology. In particular, he has generated novel genetic and chemical genetic mouse models as well as employed mouse models of disease to define the action of GPCR targeted drugs in the regulation and modification of human diseases including neurodegeneration.

During this time Andrew became interested in employing the pharmacological principles and the technologies developed in the GPCR work to the question of probing essential pathways in the malaria parasite with the aim of developing novel therapeutics. In this work he has focused on protein phosphorylation and described for the first time the essential protein kinases in the human malarial parasite P. falciparum. His group were among the first to publish the global phospho-proteome of the malarial parasite. He is now developing novel protein kinases inhibitors that selectively target essential parasite kinases with the aim of generating next generation anti-malarial’s.

Now at the University of Glasgow Andrew has established the Centre for Translational Pharmacology aimed at drawing together his interests in GPCRs and protein kinases into a Centre focused on defining the novel paradigms in pharmacology that will allow for the rational design of next generation drugs.

Research interests

The Tobin laboratory has two primary areas of research. The first is our long-standing interest in G protein coupled receptor (GPCR) research which has spanned more than two decades. Primarily, focused on understanding how mechanisms of receptor post-translational modification regulate GPCR signalling in vitro and in vivo the group have used novel genetic mouse strains, mouse disease models and novel pharmacological entities to probe the function and therapeutic potential of targeting an array of GPCRs.

The second area of focus of the Tobin laboratory has been our relatively recent application of proteomic, cell biological, chemical genetic and pharmacological approaches to defining the essential phospho-signalling cascades in malaria and how to target these in the development of next generation anti-malarials.

Layman’s summary:
“We have for many years been studying the way drugs work and how we might design better drugs to treat human disease in the future. We have focused much of our work on a group of proteins that are present on the surface of cells and that respond to chemical messengers that are released by one cell and that activate another cell. These proteins are called receptors and although many drugs currently on the market, such as anti-histamines for allergies and beta-blockers for heart disease, target these receptor proteins, largely drug discovery efforts in this area fail. We are using an array of new technologies that include genetically engineered mice, to work out why these drug discovery projects fail and how we might overcome these failures in the future to make better drugs.

In concert with these studies is our work to inhibit processes in the human malarial parasite that are essential for the survival of the parasite. In these studies, we are specifically investigating the role of a universal biochemical process called protein phosphorylation that we have discovered is essential for parasite survival. By developing inhibitors that will stop protein phosphorylation in the parasite we hope to make the next generation of anti-malarials.”

Team Tobin Impact in 60 seconds video

Research interests - further information
Centre for Translational Pharmacology
Molecular Pharmacology

Publications

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Number of items: 55.

2020

Marti-Solano, M. et al. (2020) Combinatorial expression of GPCR isoforms affects signalling and drug responses. Nature, (doi: 10.1038/s41586-020-2888-2) (PMID:33149304) (Early Online Publication)

Mahindra, A., Janha, O., Mapesa, K., Sanchez Azqueta, A., Alam, M. M. , Amambua-Ngwa, A., Nwakanma, D. C., Tobin, A. B. and Jamieson, A. G. (2020) Development of potent PfCLK3 inhibitors based on TCMDC-135051 as a new class of antimalarials. Journal of Medicinal Chemistry, 63(17), pp. 9300-9315. (doi: 10.1021/acs.jmedchem.0c00451) (PMID:32787140) (PMCID:PMC7497403)

Marsango, S., Barki, N., Jenkins, L. , Tobin, A. B. and Milligan, G. (2020) Therapeutic validation of an orphan G protein-coupled receptor: the case of GPR84. British Journal of Pharmacology, (doi: 10.1111/bph.15248) (PMID:32869860) (Early Online Publication)

Scammells, P. J. et al. (2020) Development of novel 4‐arylpyridin‐2‐one and 6‐arylpyrimidin‐4‐one positive allosteric modulators of the M1 muscarinic acetylcholine receptor. ChemMedChem, (doi: 10.1002/cmdc.202000540) (Early Online Publication)

Quon, T., Lin, L.-C., Ganguly, A., Tobin, A. B. and Milligan, G. (2020) Therapeutic opportunities and challenges in targeting the orphan G protein-coupled receptor GPR35. ACS Pharmacology and Translational Science, 3(5), pp. 801-812. (doi: 10.1021/acsptsci.0c00079) (PMID:33073184)

Vanaerschot, M. et al. (2020) Inhibition of resistance-refractory P. falciparum kinase PKG delivers prophylactic, blood stage, and transmission-blocking antiplasmodial activity. Cell Chemical Biology, 27(7), 806-816.e8. (doi: 10.1016/j.chembiol.2020.04.001) (PMID:32359426) (PMCID:PMC7369637)

Thompson, K. J. and Tobin, A. B. (2020) Crosstalk between the M1 muscarinic acetylcholine receptor and the endocannabinoid system: A relevance for Alzheimer's disease? Cellular Signalling, 70, 109545. (doi: 10.1016/j.cellsig.2020.109545) (PMID:31978506) (PMCID:PMC7184673)

Rexen Ulven, E. et al. (2020) Structure-activity relationship studies of tetrahydroquinolone free fatty acid receptor 3 modulators. Journal of Medicinal Chemistry, 63(7), pp. 3577-3595. (doi: 10.1021/acs.jmedchem.9b02036) (PMID:32141297) (PMCID:PMC7307922)

Tobin, A. B. and Bradley, S. J. (2020) Editorial for Advances in G Protein-Coupled Receptor Signal Transduction Special Issue. ACS Pharmacology and Translational Science, 3(2), pp. 169-170. (doi: 10.1021/acsptsci.0c00029) (PMID:32296759)

Bradley, S. J. et al. (2020) Biased M1-muscarinic-receptor-mutant mice inform the design of next-generation drugs. Nature Chemical Biology, 16(3), pp. 240-249. (doi: 10.1038/s41589-019-0453-9) (PMID:32080630)

2019

Vuckovic, Z. et al. (2019) Crystal structure of the M5 muscarinic acetylcholine receptor. Proceedings of the National Academy of Sciences of the United States of America, 116(51), pp. 26001-26007. (doi: 10.1073/pnas.1914446116) (PMID:31772027) (PMCID:PMC6926013)

Alam, M. M. et al. (2019) Validation of the protein kinase PfCLK3 as a multistage cross-species malarial drug target. Science, 365(6456), eaau1682. (doi: 10.1126/science.aau1682)

Thompson, K.J., Khajehali, E., Molloy, C. , Valant, C., Bradley, S.J. , Sexton, P.M., Christopoulos, A. and Tobin, A.B. (2019) The In Vitro Characterisation of DREADD Agonist 21, a Novel Ligand for Muscarinic DREADD Receptors. British Journal of Pharmacology 176(16): 3002-3003. Selected Abstract from Pharmacology 2018, London, UK, 18-20 Dec 2018. (doi:10.1111/bph.14681)

Bolognini, D. et al. (2019) Chemogenetics defines receptor-mediated functions of short chain free fatty acids. Nature Chemical Biology, 15(5), pp. 489-498. (doi: 10.1038/s41589-019-0270-1) (PMID:30992568)

Mackenzie, A. E., Quon, T., Lin, L.-C., Hauser, A. S., Jenkins, L. , Inoue, A., Tobin, A. B. , Gloriam, D. E., Hudson, B. D. and Milligan, G. (2019) Receptor selectivity between the G proteins Gα12 and Gα13 is defined by a single leucine-to-isoleucine variation. FASEB Journal, 33(4), pp. 5005-5017. (doi: 10.1096/fj.201801956R) (PMID:30601679) (PMCID:PMC6436656)

Jörg, M. et al. (2019) 6-Phenylpyrimidin-4-ones as positive allosteric modulators at the M1 mAChR: the determinants of allosteric activity. ACS Chemical Neuroscience, 10(3), pp. 1099-1114. (doi: 10.1021/acschemneuro.8b00613) (PMID:30547573)

Mancini, S., Mahmud, Z. A., Jenkins, L. , Bolognini, D., Newman, R., Barnes, M., Edye, M. E., McMahon, S. B., Tobin, A. B. and Milligan, G. (2019) On-target and off-target effects of novel orthosteric and allosteric activators of GPR84. Scientific Reports, 9, 1861. (doi: 10.1038/s41598-019-38539-1) (PMID:30755705) (PMCID:PMC6372602)

Müskens, F. M., Ward, R. J., Herkt, D., van de Langemheen, H., Tobin, A. B. , Liskamp, R. M.J. and Milligan, G. (2019) Design, synthesis and evaluation of a diazirine photoaffinity probe for ligand-based receptor capture targeting G protein-coupled receptors. Molecular Pharmacology, 95(2), pp. 196-209. (doi: 10.1124/mol.118.114249) (PMID:30514721) (PMCID:PMC6324650)

2018

Thompson, K. J. et al. (2018) DREADD agonist 21 is an effective agonist for muscarinic-based DREADDs in vitro and in vivo. ACS Pharmacology and Translational Science, 1(1), pp. 61-72. (doi: 10.1021/acsptsci.8b00012) (PMID:30868140) (PMCID:PMC6407913)

Bourgognon, J.-M. , Spiers, J. G., Scheiblich, H., Antonov, A., Bradley, S. J. , Tobin, A. B. and Steinert, J. R. (2018) Alterations in neuronal metabolism contribute to the pathogenesis of prion disease. Cell Death and Differentiation, 25(8), pp. 1408-1425. (doi: 10.1038/s41418-018-0148-x) (PMID:29915278) (PMCID:PMC6113283)

Khajehali, E., Valant, C., Jörg, M., Tobin, A. B. , Conn, P. J., Lindsley, C. W., Sexton, P. M., Scammells, P. J. and Christopoulos, A. (2018) Probing the binding site of novel selective positive allosteric modulators at the M1 muscarinic acetylcholine receptor. Biochemical Pharmacology, 154, pp. 243-254. (doi: 10.1016/j.bcp.2018.05.009) (PMID:29777683) (PMCID:PMC6066355)

Bradley, S. J. , Tobin, A. B. and Prihandoko, R. (2018) Muscarinic acetylcholine receptors in the central nervous system. Neuropharmacology, 136(Part C), p. 361. (doi: 10.1016/j.neuropharm.2018.06.012) (PMID:29894772)

van der Westhuizen, E. T. et al. (2018) Assessment of the molecular mechanisms of action of novel 4-phenylpyridine-2-one and 6-phenylpyrimidin-4-one allosteric modulators at the M1 muscarinic acetylcholine receptors. Molecular Pharmacology, 94(1), pp. 770-783. (doi: 10.1124/mol.118.111633) (PMID:29691279)

Bradley, S. J. , Tobin, A. B. and Prihandoko, R. (2018) The use of chemogenetic approaches to study the physiological roles of muscarinic acetylcholine receptors in the central nervous system. Neuropharmacology, 136(Part C), pp. 421-426. (doi: 10.1016/j.neuropharm.2017.11.043) (PMID:29191752)

Bradley, S. J. et al. (2018) Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes. Molecular Pharmacology, 93(6), pp. 645-656. (doi: 10.1124/mol.118.111872) (PMID:29695609) (PMCID:PMC5963591)

2017

Milligan, G. , Alvarez-Curto, E. , Hudson, B. D. , Prihandoko, R. and Tobin, A. B. (2017) FFA4/GPR120: pharmacology and therapeutic opportunities. Trends in Pharmacological Sciences, 38(9), pp. 809-821. (doi: 10.1016/j.tips.2017.06.006) (PMID:28734639) (PMCID:PMC5582618)

Bradley, S. J. et al. (2017) M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss. Journal of Clinical Investigation, 127(2), pp. 487-499. (doi: 10.1172/JCI87526) (PMID:27991860) (PMCID:PMC5272187)

2016

Alvarez-Curto, E. , Inoue, A., Jenkins, L. , Raihan, S. Z., Prihandoko, R., Tobin, A. B. and Milligan, G. (2016) Targeted elimination of G proteins and arrestins defines their specific contributions to both intensity and duration of G protein-coupled receptor signalling. Journal of Biological Chemistry, 291(53), pp. 27147-27159. (doi: 10.1074/jbc.M116.754887) (PMID:27852822) (PMCID:PMC5207144)

Mitcheson, D. F. et al. (2016) A new tool for the chemical genetic investigation of the Plasmodium falciparum Pfnek-2 NIMA-related kinase. Malaria Journal, 15(1), 535. (doi: 10.1186/s12936-016-1580-3) (PMID:27821169) (PMCID:PMC510031)

Zindel, D., Engel, S., Bottrill, A. R., Pin, J.-P., Prézeau, L., Tobin, A. B. , Bünemann, M., Krasel, C. and Butcher, A. J. (2016) Identification of key phosphorylation sites in PTH1R that determine arrestin3 binding and fine-tune receptor signaling. Biochemical Journal, 473(22), pp. 4173-4192. (doi: 10.1042/bcj20160740) (PMID:27623777) (PMCID:PMC5103873)

Bolognini, D. et al. (2016) A novel allosteric activator of free fatty acid 2 receptor displays unique Gi-functional bias. Journal of Biological Chemistry, 291, pp. 18915-18931. (doi: 10.1074/jbc.M116.736157) (PMID:27385588) (PMCID:PMC5009265)

Butcher, A. J. et al. (2016) An antibody biosensor establishes the activation of the M1 muscarinic acetylcholine receptor during learning and memory. Journal of Biological Chemistry, 291(17), pp. 8862-8875. (doi: 10.1074/jbc.M115.681726) (PMID:26826123) (PMCID:PMC4861454)

Bradley, S. J. et al. (2016) Mapping physiological G protein-coupled receptor signaling pathways reveals a role for receptor phosphorylation in airway contraction. Proceedings of the National Academy of Sciences of the United States of America, 113(16), pp. 4524-4529. (doi: 10.1073/pnas.1521706113) (PMID:27071102) (PMCID:PMC4843461)

Nuber, S., Zabel, U., Lorenz, K., Nuber, A., Milligan, G. , Tobin, A. B. , Lohse, M. J. and Hoffmann, C. (2016) β-Arrestin biosensors reveal a rapid, receptor-dependent activation/deactivation cycle. Nature, 531, pp. 661-664. (doi: 10.1038/nature17198) (PMID:27007855)

Bouzo-Lorenzo, M., Santo-Zas, I., Lodeiro, M., Nogueiras, R., Casanueva, F. F., Castro, M., Pazos, Y., Tobin, A. B. , Butcher, A. J. and Camiña, J. P. (2016) Distinct phosphorylation sites on the ghrelin receptor, GHSR1a, establish a code that determines the functions of ß-arrestins. Scientific Reports, 6, p. 22495. (doi: 10.1038/srep22495) (PMID:26935831) (PMCID:PMC4776146)

Bolognini, D., Tobin, A. B. , Milligan, G. and Moss, C. E. (2016) The pharmacology and function of receptors for short-chain fatty acids. Molecular Pharmacology, 89(3), pp. 388-398. (doi: 10.1124/mol.115.102301) (PMID:26719580)

Bradley, S. J. and Tobin, A. B. (2016) Design of next-generation G protein–coupled receptor drugs: linking novel pharmacology and in vivo animal models. Annual Review of Pharmacology and Toxicology, 56(1), pp. 535-559. (doi: 10.1146/annurev-pharmtox-011613-140012) (PMID:26738479)

Prihandoko, R., Alvarez-Curto, E. , Hudson, B. D. , Butcher, A. J., Ulven, T., Miller, A. M., Tobin, A. B. and Milligan, G. (2016) Distinct phosphorylation clusters determines the signalling outcome of the free fatty acid receptor FFA4/GPR120. Molecular Pharmacology, 89(5), pp. 505-520. (doi: 10.1124/mol.115.101949) (PMID:26873857)

2015

Rossi, M. et al. (2015) CK2 acts as a potent negative regulator of receptor-mediated insulin release in vitro and in vivo. Proceedings of the National Academy of Sciences of the United States of America, 112(49), E6818-E6824. (doi: 10.1073/pnas.1519430112) (PMID:26598688) (PMCID:PMC4679045)

Schrage, R. et al. (2015) The experimental power of FR900359 to study Gq-regulated biological processes. Nature Communications, 6, p. 10156. (doi: 10.1038/ncomms10156) (PMID:26658454) (PMCID:PMC4682109)

Brochet, M., Tobin, A. B. , Billker, O. and Doerig, C. (2015) The kinomics of malaria. In: Kraatz, H.-B. and Martic, S. (eds.) Kinomics: Approaches and applications. Wiley-VCH: Weinheim, pp. 115-136. ISBN 9783527337651 (doi:10.1002/9783527683031.ch5)

Mitcheson, D. F., Tobin, A. B. and Alam, M. M. (2015) Applying chemical genetic tools to the study of phospho-signalling pathways in malaria parasites. Biochimica et Biophysica Acta: Proteins and Proteomics, 1854(10), pp. 1650-1656. (doi: 10.1016/j.bbapap.2015.06.014) (PMID:26143498)

Willars, G. B., Tobin, A. B. and Challiss, R.A. J. (2015) British Pharmacological Society, 5th Focused Meeting on Cell Signalling: Matters arising …. British Journal of Pharmacology, 172(13), pp. 3194-3195. (doi: 10.1111/bph.13171) (PMID:26095874) (PMCID:PMC4500359)

Prihandoko, R., Bradley, S. J. , Tobin, A. and Butcher, A. J. (2015) Determination of GPCR phosphorylation status: establishing a phosphorylation barcode. Current Protocols in Pharmacology, 69, 2.13.1-2.13.26. (doi: 10.1002/0471141755.ph0213s69) (PMID:26344213)

Doerig, C., Rayner, J. C., Scherf, A. and Tobin, A. B. (2015) Post-translational protein modifications in malaria parasites. Nature Reviews Microbiology, 13(3), pp. 160-172. (doi: 10.1038/nrmicro3402) (PMID:25659318)

Zindel, D., Butcher, A. J., Al-Sabah, S., Lanzerstorfer, P., Weghuber, J., Tobin, A. B. , Bunemann, M. and Krasel, C. (2015) Engineered hyperphosphorylation of the 2-adrenoceptor prolongs arrestin-3 binding and induces arrestin internalization. Molecular Pharmacology, 87(2), pp. 349-362. (doi: 10.1124/mol.114.095422) (PMID:25425623) (PMCID:PMC4293452)

Alam, M. M. et al. (2015) Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion. Nature Communications, 6, 7285. (doi: 10.1038/ncomms8285) (PMID:26149123) (PMCID:PMC4507021)

2014

Kern, S. et al. (2014) Inhibition of the SR protein-phosphorylating CLK kinases of plasmodium falciparum impairs blood stage replication and malaria transmission. PLoS ONE, 9(9), e105732. (doi: 10.1371/journal.pone.0105732) (PMID:25188378) (PMCID:PMC415485)

Tobin, A. and Prihandoko, R. (2014) Reply to "Letter to the editor: 'Systems biology versus reductionism in cell physiology'". American Journal of Physiology: Cell Physiology, 307(3), C310-C310. (doi: 10.1152/ajpcell.00192.2014) (PMID:25088763) (PMCID:PMC4121582)

Prihandoko, R. and Tobin, A. B. (2014) Challenges of assigning protein kinases to in vivo phosphorylation events. Focus on "Use of LC-MS/MS and Bayes' theorem to identify protein kinases that phosphorylate aquaporin-2 at Ser256". American Journal of Physiology: Cell Physiology, 307(2), C121-C122. (doi: 10.1152/ajpcell.00136.2014) (PMID:24829494)

Butcher, A. J., Hudson, B. D. , Shimpukade, B., Alvarez-Curto, E. , Prihandoko, R., Ulven, T., Milligan, G. and Tobin, A. B. (2014) Concomitant action of structural elements and receptor phosphorylation determine arrestin-3 interaction with the free fatty acid receptor FFA4. Journal of Biological Chemistry, 289, pp. 18451-18465. (doi: 10.1074/jbc.M114.568816) (PMID:24817122) (PMCID:PMC4140278)

Bradley, S. J. , Riaz, S. A. and Tobin, A. (2014) Employing novel animal models in the design of clinically efficacious GPCR ligands. Current Opinion in Cell Biology, 27, pp. 117-125. (doi: 10.1016/j.ceb.2013.12.002) (PMID:24680437) (PMCID:PMC3989050)

Graciotti, M., Alam, M. , Solyakov, L., Schmid, R., Burley, G., Bottrill, A. R., Doerig, C., Cullis, P. and Tobin, A. B. (2014) Malaria protein kinase CK2 (PfCK2) shows novel mechanisms of regulation. PLoS ONE, 9(3), e85391. (doi: 10.1371/journal.pone.0085391) (PMID:24658579) (PMCID:PMC3962329)

2012

Lasonder, E., Treeck, M., Alam, M. and Tobin, A. B. (2012) Insights into the Plasmodium falciparum schizont phospho-proteome. Microbes and Infection, 14(10), pp. 811-819. (doi: 10.1016/j.micinf.2012.04.008) (PMID:22569589)

2011

Solyakov, L. et al. (2011) Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum. Nature Communications, 2, 565. (doi: 10.1038/ncomms1558) (PMID:22127061)

This list was generated on Wed Nov 25 12:24:15 2020 GMT.

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