AgreenSkills session, year: 1st session, 2014
Receiving laboratory: PRC Reproductive and Behavioural Physiology Tours, Val de Loire - Nouzilly, France
Country of origin : Saudi Arabia
Identification and Pharmacological Profiling of Selective Nanobodies Targeting - G Protein-Coupled Receptors – Towards in vivo Applications
My project aims to develop new generation of biologicals targeting GPCRs. These biologicals are antibody fragments generated from camelids, called nanobodies. I am in charge of developing a battery of molecular, biochemical, and signalling assays that will be instrumental for the development of the nanobodies. Indeed, nanobodies displaying distinct activation profiles are expected: activators versus inhibitors, full versus partial activities, competitors versus allosteric binders,… Each profile could potentially lead to valuable in vivo action; therefore accurate screening and characterization will be carried out. Furthermore, the potential clinical and agronomic applications of the nanobodies will be assessed using in vivo models.
I am graduated from the University of Paris XI (France) where I obtained my Master and PhD (2000-2003) in Biochemistry and Molecular Biology. Then my research experience was strongly consolidated through a postdoctoral position in Montpellier (France)(2004-2009) and Research Assistant Professor position in Perth (Western Australia)(2009-2011). Both my PhD and postdoctoral studies were related to the study of the biology and signalling of a class of cell surface receptors named G protein-coupled receptors (GPCRs) through the development of biophysical energy transfer-based approaches (BRET and TR-FRET). These technologies allow studying the real time dynamics of molecular events triggered by GPCR activation in living cells. Overall, I have published more than 35 original articles and attended around 30 national and international meetings. My expertise in this field also allowed me to have a sustained peer-review and refereeing activities for various scientific journals and grant agencies. Moreover, I also had an interesting teaching experience in King Saud University in Riyadh (Saudi Arabia)(2012-2014) where I have been appointed as Assistant Professor in the Biochemistry Department to teach different courses such as Biomembranes and Cell Signalling, Hormones, and Biochemical Endocrinology. Since July 2014, I am double fellow of LE STUDIUM Loire Valley Institute for Advanced Studies and AgreenSkills Plus to work on the research project funded by the French Region Centre within its “Smart Loire Valley” programme on Bio-Pharmaceuticals, in the framework of the 2014-2020 Smart Specialization Strategy of the European régions.
1- Gomes I, Ayoub M.A, Fujita W, Jaeger W.C, Pfleger K.D, and Devi L.A. (2015) G Protein-Coupled Receptors Heteromers. Annula Review of Pharmacology and Toxicology (Accepted).
2- Ayoub M.A#, Zhang Y#, Kelly, R.S, See H.B, Johnstone, E.K.M, McCall E, Williams J, Kelly D.J, and Pfleger K.D.G. (2015) Functional Interaction between Angiotensin II Receptor Type 1 and Chemokine (C-C Motif) Receptor 2 with Implication for Chronic Kidney Disease. PLoS ONE 10(3): e0119803. doi:10.1371/journal.pone.0119803
3-Ayoub M.A, Trebaux J, Vallaghe J, Charrier-Savournin F, Al-Hosaini K, Gonzalez-Moya A, Pin J.P, Pfleger K.D, and Trinquet E. (2014) Homogeneous Time-Resolved Fluorescence-Based Assay to Monitor Extracellular Signal-Regulated Kinase Signalling in a High-Throughput Format. Frontiers in Molecular and Structural Endocrinology 5:94. doi: 10.3389/fendo.2014.00094.
4- Ayoub M.A and Pin J.P. (2013) Interaction of Protease-Activated Receptor 2 with G Proteins and b-arrestin 1 Studied by Bioluminescence Resonance Energy Transfer. Frontiers in Molecular and Structural Endocrinology 4:196. doi: 10.3389/fendo.2013.00196.
5-Ayoub M.A. (2013) The Nobel Prize in Chemistry 2012, G Protein-Coupled Receptors, Rightly Rewarded. Arabian Journal of Chemistry doi: http://dx.doi.org/10.1016/j.arabjc.2013.08.020.
6-Ayoub M.A, See H.B, Seeber R.M, Armstrong S.P, and Pfleger K.D.G. (2013) Profiling Epidermal Growth Factor Receptor and Heregulin Receptor 3 Heteromerization Using Receptor Tyrosine Kinase Heteromer Investigation Technology. PLoS ONE 8(5): e64672.
7-Ayoub M.A, Al-Senaidy A, and Pin J.P. (2012) Receptor-G Protein Interaction Studied by Bioluminescence Resonance Energy Transfer: Lessons From Protease-Activated Receptor 1. Frontiers in Molecular and Structural Endocrinology 3: 82.
8-Ayoub M.A, Angelicheva D, Vile D, Chandler D, Morar B, Cavanaugh J.A, Visscher P.M, Jablensky A, Pfleger K.D.G, and Kalaydjieva L. (2012) Deleterious GRM1 Mutations in Schizophrenia. PLoS ONE 7(3): e32849.
9-Ayoub M.A, Trinquet E, Pfleger K.D.G, and Pin J.P. (2010) Differential association modes of the thrombin receptor PAR1 with Gai1, Ga12 and b-arrestin 1. The FASEB Journal 24(9): 3522-3535.
10-Ayoub M.A and Pfleger K.D.G. (2010) Recent advances in bioluminescence resonance energy transfer technologies to study GPCR heteromerization. Current Opinion in Pharmacology 10(1): 44-52.
11-Tenenbaum J, Ayoub M.A, Perkovska S, Adra-Delenne A.L, Mendre C, Ranchin B, Bricca G, Geelen G, Mouillac B, Durroux T, and Morin M. (2009) The constitutively active V2 receptor mutants conferring NSIAD are weakly sensitive to agonist and antagonist regulation. PLoS ONE 4(12): e8383.
12-Ayoub M.A, Damian M, Gespach C, Ferrandis E, Lavergne O, De Wever O, Banères J.L, Pin J.P, and Prévost G.P. (2009) Inhibition of Heterotrimeric G Protein Signaling by a Small Molecule Acting on Galpha Subunit. The Journal of Biological Chemistry 284(42): 29136-29145.
13-Maurel D, Comps-Agrar L, Brock C, Rives M.L, Bourrier E, Ayoub M.A, Bazin H, Tinel N, Durroux T, Prézeau L, Trinquet E, and Pin J.P. (2008) Cell surface protein-protein interaction analysis with time-resolved FRET and snap-tag technologies: application to GPCR oligomerization. Nature Methods 5(6): 561-567
14-Ayoub M.A, Maurel D, Binet V, Fink M, Prézeau L, Ansanay H, and Pin J.P. (2007) Real-time analysis of agonist-induced activation of Protease-activated receptor 1/Gai1 protein complex measured by BRET in living cells. Molecular Pharmacology 71(5): 1329-1340.
15-Levoye A, Dam J, Ayoub M.A, Guillaume J.L, Couturier C, Delagrange P, and Jockers R. (2006) The orphan GPR50 receptor specifically antagonizes MT1 melatonin receptor function through heterodimerization. The EMBO Journal 25(13): 3012-23. (Impact factor: 9.82, citations: 133)
16-Ayoub M.A, Levoye A, Delagrange P, and Jockers R. (2004) Preferential Formation of MT1/MT2 Melatonin Receptor Heterodimers With Distinct Ligand Interaction Properties Compared With MT2 Homodimers. Molecular Pharmacology 66(2): 312-321
17-Ayoub M.A, Couturier C, Lucas-Meunier E, Angers S, Fossier P, Bouvier M, and Jockers R. (2002) Monitoring of ligand-independent dimerization and ligand-induced conformational changes of melatonin receptors in living cells by bioluminescence resonance energy transfer. The Journal of Biological Chemistry 277(24): 21522-21528.
- Travel Award of GDR GPCR-DiscoveRx – DiscoveRx European GPCR Technology Symposuim. “Elucidating GPCR Functional Selectivity and Biased Agonism: Novel Opportunities for Drug Development”. 12 May 2015 – Cambridge, UK.
- AgreenSkills+ Fellowship – 1st Selection round 2014 (funding duration: 36 months).
- The International Meeting Travel Grant of King Saud University to attend “The Gordon Conference – Molecular Pharmacology”. 28 April – 03 May 2013 – II Ciocco, Lucca, Italy.
- The Supplementary Travel Grant of the University of Western Australia to support my participation to “The VIth Annual Meeting of the Molecular Pharmacology of G Protein-Coupled Receptors”: 2-4 December 2010 – Melbourne, Australia.
- Travel Award of “The Gordon Conference – Molecular Pharmacology”: 31 May- 5 June 2009 – II Ciocco, Lucca, Italy.
- The XIth European Pineal and Biological Rhythms Society Symposium: 18-23 July 2002 – Aberdeen, Scotland.
- Naturalia & Biologia travel award to attend the XXXIVth Congress of the International Union of Physiological Sciences. 21-23 August 2001 – Adelaide, Australia.