Mrs Laura Jenkins
- Technical Specialist/Lab Manager (Molecular Biosciences)
telephone:
01413306483
email:
Laura.Jenkins@glasgow.ac.uk
University of Glasgow, Mvls, Wolfson Link Bldg - Lab 253, Glasgow G12 8QQ
https://orcid.org/0000-0003-1382-8547Biography
Key Skills
Core Funded
- Cell Culture: maintain cell lines, transfection, generate stable cell lines, dissection and culture of primary neurons
- Molecular biology technique: PCR and RT-PCR, RNA and DNA extraction, gel electrophoresis, subcloning, site-directed mutagenesis, western blotting
- Functional assays: 35S GTPys, cAMP, IPone, BRET assay, calcium mobilisation experiments
- Radioligand binding: saturation and competition binding, kinetic experiments
- Microscopy: bright-field and epifluoresence microscopy, live cell imaging, immunocytochemistry
- Drug discovery: optimisation and validation of cell based assays for high-throughput screens, handing and analysis of large data sets and spreadsheets
- Health and Safety: generate and review lab COSHH forms, create radioisotope risk assessments
Research interests
Within our Molecular Pharmacology group, focus is on the structure, function and regulation of G protein-coupled receptors (GPCRs) and their interacting proteins. A large part of my role within the group is driving forward drug discovery programmes that Professor Milligan has with industrial partners, aiming to identify novel ligands at orphan GPCRs.
Publications
2022
Mahindra, A. et al. (2022) Investigating the structure–activity relationship of 1,2,4-triazine G-protein-coupled receptor 84 (GPR84) antagonists. Journal of Medicinal Chemistry, (doi: 10.1021/acs.jmedchem.2c00804) (PMID:35948061) (Early Online Publication)
Marsango, S., Barki, N., Jenkins, L. , Tobin, A. B. and Milligan, G. (2022) Therapeutic validation of an orphan G protein-coupled receptor: the case of GPR84. British Journal of Pharmacology, 179(14), pp. 3529-3541. (doi: 10.1111/bph.15248) (PMID:32869860)
Marsango, S. et al. (2022) The M1 muscarinic receptor is present in situ as a ligand-regulated mixture of monomers and oligomeric complexes. Proceedings of the National Academy of Sciences of the United States of America, 119(24), e220110311. (doi: 10.1073/pnas.2201103119) (PMID:35671422) (PMCID:PMC9214538)
Marsango, S. et al. (2022) Selective phosphorylation of threonine residues defines GPR84-arrestin interactions of biased ligands. Journal of Biological Chemistry, 298(5), 101932. (doi: 10.1016/j.jbc.2022.101932) (PMID:35427647) (PMCID:PMC9118924)
Barki, N. et al. (2022) Chemogenetics defines the roles of short chain fatty acid receptors within the gut-brain axis. eLife, 11, e73777. (doi: 10.7554/eLife.73777) (PMID:35229717)
Divorty, N., Jenkins, L. , Ganguly, A., Butcher, A. J., Hudson, B. D. , Schulz, S., Tobin, A. B. , Nicklin, S. A. and Milligan, G. (2022) Agonist-induced phosphorylation of orthologues of the orphan receptor GPR35 functions as an activation sensor. Journal of Biological Chemistry, 298(3), 101655. (doi: 10.1016/j.jbc.2022.101655) (PMID:35101446) (PMCID:PMC8892012)
2021
Scarpa, M. et al. (2021) Biased M1 muscarinic receptor mutant mice show accelerated progression of prion neurodegenerative disease. Proceedings of the National Academy of Sciences of the United States of America, 118(50), e2107389118. (doi: 10.1073/pnas.2107389118) (PMID:34893539) (PMCID:PMC8685681)
Milligan, G. et al. (2021) Discovery and characterization of novel antagonists of the proinflammatory orphan receptor GPR84. ACS Pharmacology and Translational Science, 4(5), pp. 1598-1613. (doi: 10.1021/acsptsci.1c00151) (PMID:34661077) (PMCID:PMC8506611)
Boleij, A. et al. (2021) G-protein coupled receptor 35 (GPR35) regulates the colonic epithelial cell response to enterotoxigenic Bacteroides fragilis. Communications Biology, 4, 585. (doi: 10.1038/s42003-021-02014-3) (PMID:33990686) (PMCID:PMC8121840)
2020
Labéguère, F. et al. (2020) Discovery of 9-Cyclopropylethynyl-2-((S)-1-[1,4]dioxan-2-ylmethoxy)-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one (GLPG1205), a unique GPR84 negative allosteric modulator undergoing evaluation in a phase II clinical trial. Journal of Medicinal Chemistry, 63(22), pp. 13526-13545. (doi: 10.1021/acs.jmedchem.0c00272) (PMID:32902984)
2019
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)
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)
2018
Binti Mohd Amir, N. A.S., Mackenzie, A. E., Jenkins, L. , Boustani, K., Hillier, M. C., Tsuchiya, T., Milligan, G. and Pease, J. E. (2018) Evidence for the existence of a CXCL17 receptor distinct from GPR35. Journal of Immunology, 201(2), pp. 714-724. (doi: 10.4049/jimmunol.1700884) (PMID:29875152) (PMCID:PMC6036231)
2017
Mahmud, Z. A., Jenkins, L. , Ulven, T., Labéguère, F., Gosmini, R., De Vos, S., Hudson, B. D. , Tikhonova, I. G. and Milligan, G. (2017) Three classes of ligands each bind to distinct sites on the orphan G protein-coupled receptor GPR84. Scientific Reports, 7, 17953. (doi: 10.1038/s41598-017-18159-3) (PMID:29263400) (PMCID:PMC5738391)
Kaspersen, M. H., Jenkins, L. , Dunlop, J. , Milligan, G. and Ulven, T. (2017) Succinct synthesis of saturated hydroxy fatty acids and in vitro evaluation of all hydroxylauric acids on FFA1, FFA4 and GPR84. MedChemComm, 8(6), pp. 1360-1365. (doi: 10.1039/c7md00130d)
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)
2015
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)
Christiansen, E. et al. (2015) Activity of dietary fatty acids on FFA1 and FFA4 and characterisation of pinolenic acid as a dual FFA1/FFA4 agonist with potential effect against metabolic diseases. British Journal of Nutrition, 113(11), pp. 1677-1688. (doi: 10.1017/S000711451500118X) (PMID:25916176)
2014
Hudson, B. D. , Christiansen, E., Murdoch, H., Jenkins, L. , Hansen, A. H., Madsen, O., Ulven, T. and Milligan, G. (2014) Complex pharmacology of novel allosteric free fatty acid 3 receptor ligands. Molecular Pharmacology, 86(2), pp. 200-210. (doi: 10.1124/mol.114.093294)
Mackenzie, A.E. et al. (2014) The antiallergic mast cell stabilizers lodoxamide and bufrolin as the first high and equipotent agonists of human and rat gpr35. Molecular Pharmacology, 85(1), pp. 91-104. (doi: 10.1124/mol.113.089482)
2013
Christiansen, E. et al. (2013) Discovery of TUG-770: a highly potent free fatty acid receptor 1 (FFA1/GPR40) agonist for treatment of type 2 diabetes. ACS Medicinal Chemistry Letters, 4(5), pp. 441-445. (doi: 10.1021/ml4000673)
Jenkins, L. , Harries, N., Lappin, J.E., MacKenzie, A.E., Neetoo-Isseljee, Z., Southern, C., McIver, E.G., Nicklin, S.A. , Taylor, D.L. and Milligan, G. (2013) Antagonists of GPR35 display high species ortholog selectivity and varying modes of action. Journal of Pharmacology and Experimental Therapeutics, 343(3), pp. 683-695. (doi: 10.1124/jpet.112.198945) (PMID:22967846) (PMCID:PMC3500541)
2010
Jenkins, L. , Alvarez-Curto, E. , Campbell, K., De Munnik, S., Canals Buj, M., Schlyer, S. and Milligan, G. (2010) Agonist activation of the G protein-coupled receptor GPR35 involves transmembrane domain III and is transduced via Gα13 and β-arrestin-2. British Journal of Pharmacology, 162(3), pp. 733-748. (doi: 10.1111/j.1476-5381.2010.01082.x)
Jenkins, L. , Brea, J., Smith, N.J., Hudson, B.D. , Reilly, G., Bryant, N.J., Castro, M., Loza, M.I. and Milligan, G. (2010) Identification of novel species-selective agonists of the G-protein-coupled receptor GPR35 that promote recruitment of β-arrestin-2 and activate Gα13. Biochemical Journal, 432(3), pp. 451-459. (doi: 10.1042/BJ20101287)
2009
Smith, N.J., Stoddart, L.A., Devine, N.M., Jenkins, L. and Milligan, G. (2009) The action and mode of binding of thiazolidinedione ligands at free fatty acid receptor 1. Journal of Biological Chemistry, 284(26), pp. 17527-17539. (doi: 10.1074/jbc.M109.012849) (PMID:19398560) (PMCID:PMC2719392)
Ward, R. J., Jenkins, L. and Milligan, G. (2009) Selectivity and functional consequences of interactions of family A G protein-coupled receptors with neurochondrin and periplakin. Journal of Neurochemistry, 109(1), pp. 182-192. (doi: 10.1111/j.1471-4159.2009.05918.x)
2008
Stoddart, L. A., Smith, N. J., Jenkins, L. , Brown, A. J. and Milligan, G. (2008) Conserved Polar Residues in Transmembrane Domains V, VI, and VII of Free Fatty Acid Receptor 2 and Free Fatty Acid Receptor 3 Are Required for the Binding and Function of Short Chain Fatty Acids. Journal of Biological Chemistry, 283(47), pp. 32913-32924. (doi: 10.1074/jbc.M805601200) (PMID:18801738)
Articles
Mahindra, A. et al. (2022) Investigating the structure–activity relationship of 1,2,4-triazine G-protein-coupled receptor 84 (GPR84) antagonists. Journal of Medicinal Chemistry, (doi: 10.1021/acs.jmedchem.2c00804) (PMID:35948061) (Early Online Publication)
Marsango, S., Barki, N., Jenkins, L. , Tobin, A. B. and Milligan, G. (2022) Therapeutic validation of an orphan G protein-coupled receptor: the case of GPR84. British Journal of Pharmacology, 179(14), pp. 3529-3541. (doi: 10.1111/bph.15248) (PMID:32869860)
Marsango, S. et al. (2022) The M1 muscarinic receptor is present in situ as a ligand-regulated mixture of monomers and oligomeric complexes. Proceedings of the National Academy of Sciences of the United States of America, 119(24), e220110311. (doi: 10.1073/pnas.2201103119) (PMID:35671422) (PMCID:PMC9214538)
Marsango, S. et al. (2022) Selective phosphorylation of threonine residues defines GPR84-arrestin interactions of biased ligands. Journal of Biological Chemistry, 298(5), 101932. (doi: 10.1016/j.jbc.2022.101932) (PMID:35427647) (PMCID:PMC9118924)
Barki, N. et al. (2022) Chemogenetics defines the roles of short chain fatty acid receptors within the gut-brain axis. eLife, 11, e73777. (doi: 10.7554/eLife.73777) (PMID:35229717)
Divorty, N., Jenkins, L. , Ganguly, A., Butcher, A. J., Hudson, B. D. , Schulz, S., Tobin, A. B. , Nicklin, S. A. and Milligan, G. (2022) Agonist-induced phosphorylation of orthologues of the orphan receptor GPR35 functions as an activation sensor. Journal of Biological Chemistry, 298(3), 101655. (doi: 10.1016/j.jbc.2022.101655) (PMID:35101446) (PMCID:PMC8892012)
Scarpa, M. et al. (2021) Biased M1 muscarinic receptor mutant mice show accelerated progression of prion neurodegenerative disease. Proceedings of the National Academy of Sciences of the United States of America, 118(50), e2107389118. (doi: 10.1073/pnas.2107389118) (PMID:34893539) (PMCID:PMC8685681)
Milligan, G. et al. (2021) Discovery and characterization of novel antagonists of the proinflammatory orphan receptor GPR84. ACS Pharmacology and Translational Science, 4(5), pp. 1598-1613. (doi: 10.1021/acsptsci.1c00151) (PMID:34661077) (PMCID:PMC8506611)
Boleij, A. et al. (2021) G-protein coupled receptor 35 (GPR35) regulates the colonic epithelial cell response to enterotoxigenic Bacteroides fragilis. Communications Biology, 4, 585. (doi: 10.1038/s42003-021-02014-3) (PMID:33990686) (PMCID:PMC8121840)
Labéguère, F. et al. (2020) Discovery of 9-Cyclopropylethynyl-2-((S)-1-[1,4]dioxan-2-ylmethoxy)-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one (GLPG1205), a unique GPR84 negative allosteric modulator undergoing evaluation in a phase II clinical trial. Journal of Medicinal Chemistry, 63(22), pp. 13526-13545. (doi: 10.1021/acs.jmedchem.0c00272) (PMID:32902984)
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)
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)
Binti Mohd Amir, N. A.S., Mackenzie, A. E., Jenkins, L. , Boustani, K., Hillier, M. C., Tsuchiya, T., Milligan, G. and Pease, J. E. (2018) Evidence for the existence of a CXCL17 receptor distinct from GPR35. Journal of Immunology, 201(2), pp. 714-724. (doi: 10.4049/jimmunol.1700884) (PMID:29875152) (PMCID:PMC6036231)
Mahmud, Z. A., Jenkins, L. , Ulven, T., Labéguère, F., Gosmini, R., De Vos, S., Hudson, B. D. , Tikhonova, I. G. and Milligan, G. (2017) Three classes of ligands each bind to distinct sites on the orphan G protein-coupled receptor GPR84. Scientific Reports, 7, 17953. (doi: 10.1038/s41598-017-18159-3) (PMID:29263400) (PMCID:PMC5738391)
Kaspersen, M. H., Jenkins, L. , Dunlop, J. , Milligan, G. and Ulven, T. (2017) Succinct synthesis of saturated hydroxy fatty acids and in vitro evaluation of all hydroxylauric acids on FFA1, FFA4 and GPR84. MedChemComm, 8(6), pp. 1360-1365. (doi: 10.1039/c7md00130d)
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)
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)
Christiansen, E. et al. (2015) Activity of dietary fatty acids on FFA1 and FFA4 and characterisation of pinolenic acid as a dual FFA1/FFA4 agonist with potential effect against metabolic diseases. British Journal of Nutrition, 113(11), pp. 1677-1688. (doi: 10.1017/S000711451500118X) (PMID:25916176)
Hudson, B. D. , Christiansen, E., Murdoch, H., Jenkins, L. , Hansen, A. H., Madsen, O., Ulven, T. and Milligan, G. (2014) Complex pharmacology of novel allosteric free fatty acid 3 receptor ligands. Molecular Pharmacology, 86(2), pp. 200-210. (doi: 10.1124/mol.114.093294)
Mackenzie, A.E. et al. (2014) The antiallergic mast cell stabilizers lodoxamide and bufrolin as the first high and equipotent agonists of human and rat gpr35. Molecular Pharmacology, 85(1), pp. 91-104. (doi: 10.1124/mol.113.089482)
Christiansen, E. et al. (2013) Discovery of TUG-770: a highly potent free fatty acid receptor 1 (FFA1/GPR40) agonist for treatment of type 2 diabetes. ACS Medicinal Chemistry Letters, 4(5), pp. 441-445. (doi: 10.1021/ml4000673)
Jenkins, L. , Harries, N., Lappin, J.E., MacKenzie, A.E., Neetoo-Isseljee, Z., Southern, C., McIver, E.G., Nicklin, S.A. , Taylor, D.L. and Milligan, G. (2013) Antagonists of GPR35 display high species ortholog selectivity and varying modes of action. Journal of Pharmacology and Experimental Therapeutics, 343(3), pp. 683-695. (doi: 10.1124/jpet.112.198945) (PMID:22967846) (PMCID:PMC3500541)
Jenkins, L. , Alvarez-Curto, E. , Campbell, K., De Munnik, S., Canals Buj, M., Schlyer, S. and Milligan, G. (2010) Agonist activation of the G protein-coupled receptor GPR35 involves transmembrane domain III and is transduced via Gα13 and β-arrestin-2. British Journal of Pharmacology, 162(3), pp. 733-748. (doi: 10.1111/j.1476-5381.2010.01082.x)
Jenkins, L. , Brea, J., Smith, N.J., Hudson, B.D. , Reilly, G., Bryant, N.J., Castro, M., Loza, M.I. and Milligan, G. (2010) Identification of novel species-selective agonists of the G-protein-coupled receptor GPR35 that promote recruitment of β-arrestin-2 and activate Gα13. Biochemical Journal, 432(3), pp. 451-459. (doi: 10.1042/BJ20101287)
Smith, N.J., Stoddart, L.A., Devine, N.M., Jenkins, L. and Milligan, G. (2009) The action and mode of binding of thiazolidinedione ligands at free fatty acid receptor 1. Journal of Biological Chemistry, 284(26), pp. 17527-17539. (doi: 10.1074/jbc.M109.012849) (PMID:19398560) (PMCID:PMC2719392)
Ward, R. J., Jenkins, L. and Milligan, G. (2009) Selectivity and functional consequences of interactions of family A G protein-coupled receptors with neurochondrin and periplakin. Journal of Neurochemistry, 109(1), pp. 182-192. (doi: 10.1111/j.1471-4159.2009.05918.x)
Stoddart, L. A., Smith, N. J., Jenkins, L. , Brown, A. J. and Milligan, G. (2008) Conserved Polar Residues in Transmembrane Domains V, VI, and VII of Free Fatty Acid Receptor 2 and Free Fatty Acid Receptor 3 Are Required for the Binding and Function of Short Chain Fatty Acids. Journal of Biological Chemistry, 283(47), pp. 32913-32924. (doi: 10.1074/jbc.M805601200) (PMID:18801738)
Research datasets
2022
Marsango, S., Jenkins, L. , Pediani, J. , Bradley, S. , Ward, R., Hesse, S. and Milligan, G. (2022) The M1 muscarinic receptor is present in situ as a ligand-regulated mixture of monomers and oligomeric complexes. [Data Collection]
2021
Scarpa, M. , Molloy, C. , Jenkins, L. , Strellis, B., Budgett, R., Hesse, S. , Dwomoh, L. , Marsango, S., Tejeda, G. , Rossi, M., Ahmed, Z., Milligan, G. , Hudson, B. , Tobin, A. , Bradley, S. and Heptares, S. (2021) Biased M1 muscarinic receptor mutant mice show accelerated progression of prion neurodegenerative disease. [Data Collection]
