个人简介

Michela joined the Discipline of Chemistry at the University of Newcastle as Lecturer in January 2014. She received her BSc/Masters degree from the Victoria University of Manchester, UK. She went on to obtain her D.Phil. from the University of Oxford under the supervision of Professor George Fleet in 2006.

研究领域

Chemistry

Michela’s research interests lie under the broad umbrella of medicinal chemistry with a glycobiological spin! She is interested in the synthesis and evaluation of novel classes of glycosidase inhibitors from carbohydrate starting materials to molecular recognition and supramolecular chemistry. Recently she has also moved into the area of bioinorganic chemistry primarily as relating to cancer research, and the field of renewable energy from chemical manipulations of biomass. Carbohydrates are found ubiquitously in Nature where they represent a unique family of polyfunctional compounds which Nature extensively manipulates and finely tunes to serve a multitude of biological purposes. Carbohydrate building blocks provide a rich chiral pool of cheap, readily available and highly versatile starting materials for the enantiospecific synthesis of highly functionalised homochiral targets. They are utilised in the synthesis of many classes of compounds, including iminosugars. Iminosugars represent an important category of glycosidase inhibitors and proven to possess therapeutic potential in the management and treatment of many medical conditions, including diabetes, lysosomal storage diseases, viral infections and cancer. The amazing diversity of biological roles found within this class of small molecules is evidence of a remarkable economy of structural information in nature, which in molecular weight terms completely surpasses anything achieved by the amino acids. The Simone group is working in this burgeoning field of glycomimetics and undertaken the synthesis and evaluation of novel classes of iminosugars as anti-viral agents. Another area of active research in the group is the fluorescent tagging of proteins. It is vital to biomedicine efforts to understand the spatial and temporal underpinnings of life inside cells in vivo versus in fixed cells. Current protein fluorescent tags are plagued by many draw-backs including excessive bulk, high toxicity, the need for extensive genetic engineering and the use of covalent bonds to link the sensor to the protein under investigation. These result in their limited use in vivo. We are undertaking the fluorescent tagging of proteins via innovative strategies, namely by the use of small fluorescent supramolecular entities which are engineered to transiently and selectively bind to the protein surfaces of interest.

近期论文

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2016 Warne J, Pryce G, Hill JM, Shi X, Lennerås F, Puentes F, et al., 'Selective inhibition of the mitochondrial permeability transition pore protects against neurodegeneration in experimental multiple sclerosis', Journal of Biological Chemistry, 291 4356-4373 (2016) 2015 Cossar PJ, Hizartzidis L, Simone M, McCluskey A, Gordon CP, 'The expanding utility of continuous flow hydrogenation', Organic and Biomolecular Chemistry, 26 7119-7130 (2015) [C1] 2015 Russell C, Lin AJS, Hains P, Simone MI, Robinson PJ, Mccluskey A, 'An integrated flow and microwave approach to a broad spectrum protein kinase inhibitor', RSC Advances, 5 93433-93437 (2015) [C1] 2015 Warne J, Pryce G, Hill J, Shi X, Lenneras F, Puentes F, et al., 'Crystal structure of cyclophilin D in complex with CsA analogue, JW47. PDB Code 5A0E', RCSB Protein Databank Archive: PDB, (2015) [O1] 2014 Simone MI, Houston TA, 'A Brief Overview of Recent Advances in the Applications of Boronic Acids Relevant to Glycomics', Journal of Glycomics & Lipidomics, 04 e124 (2014) [C3] 2014 Hizartzidis L, Cossar PJ, Robertson MJ, Simone MI, Young KA, McCluskey A, Gordon CP, 'Expanding the utility of flow hydrogenation - A robust protocol restricting hydrodehalogenation', RSC Advances, 4 56743-56748 (2014) [C1] 2014 Sayer JR, Walldén K, Pesnot T, Campbell F, Gane PJ, Simone M, et al., '2- and 3-substituted imidazo[1,2-a]pyrazines as inhibitors of bacterial type IV secretion', Bioorganic and Medicinal Chemistry, 22 6459-6470 (2014) 2014 Moyes AJ, Khambata RS, Villar I, Bubb KJ, Baliga RS, Lumsden NG, et al., 'Endothelial C-type natriuretic peptide maintains vascular homeostasis', Journal of Clinical Investigation, 1 (2014) [C1] 2013 Risseeuw M, Overhand M, Fleet GWJ, Simone MI, 'A compendium of cyclic sugar amino acids and their carbocyclic and heterocyclic nitrogen analogues', Amino Acids, 45 613-689 (2013) [C1] 2013 Reed JH, Turner P, Kato A, Houston TA, Simone M, '1-O-Benzyl-2,3-O-isopropylidene-6-O-tosyl-a-L-sorbofuranose', Acta Crystallographica Section E: Structure Reports Online, 69 o1069-o1070 (2013) [C1] 2012 Dube H, Selwood D, Malouitre S, Capano M, Simone MI, Crompton M, 'A mitochondrial-targeted cyclosporin A with high binding affinity for cyclophilin D yields improved cytoprotection of cardiomyocytes', BIOCHEMICAL JOURNAL, 441 901-907 (2012) [C1] 2012 Simone MI, Soengas RG, Jenkinson SF, Evinson EL, Nash RJ, Fleet GWJ, 'Synthesis of three branched iminosugars [(3R,4R,5S)-3-(hydroxymethyl)piperidine-3,4,5-triol, (3R,4R,5R)-3-(hydroxymethyl)piperidine-3,4,5-triol and (3S,4R,5R)-3-(hydroxymethyl)piperidine-3.4,5-triol] and a branched trihydroxynipecotic acid [(3R,4R,5R)-3,4,5-trihydroxypiperidine-3-carboxylic acid] from sugar lactones with a carbon substituent at C-2', TETRAHEDRON-ASYMMETRY, 23 401-408 (2012) [C1] 2012 Soengas RG, Simone MI, Hunter S, Nash RJ, Evinson EL, Fleet GWJ, 'Hydroxymethyl-Branched Piperidines from Hydroxymethyl-Branched Lactones: Synthesis and Biological Evaluation of 1,5-Dideoxy-2-C-hydroxymethyl-1,5-imino-D-mannitol, 1,5-Dideoxy-2-C-hydroxymethyl-1,5-imino-L-gulitol and 1,5-Dideoxy-2-C-hydroxymethyl-1,5-imino-D-talitol', EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2394-2402 (2012) [C1] 2012 Jenkinson SF, Thompson AL, Simone MI, 'Methyl 2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-4-nitrobenzoate', Acta Crystallographica Section E: Structure Reports Online, 68 o2429-o2430 (2012) [C1] 2012 Gooding M, Tudzarova S, Worthington RJ, Kingsbury SR, Rebstock A-S, Dube H, et al., 'Exploring the Interaction Between siRNA and the SMoC Biomolecule Transporters: Implications for Small Molecule-Mediated Delivery of siRNA', CHEMICAL BIOLOGY & DRUG DESIGN, 79 9-21 (2012) 2011 Simone MI, Edwards AA, Tranter GE, Fleet GWJ, 'C-3 branched delta-3,5-cis- and trans-THF sugar amino acids: synthesis of the first generation of branched homooligomers', AMINO ACIDS, 41 643-661 (2011) [C1] 2010 Simone MI, Edwards AA, Parker SG, Tranter GE, Fleet GWJ, Watkin DJ, 'Pentafluorophenyl (3R,4R,5S)-5-{[(3R,4R,5S)-5-azidomethyl-3,4-dimethoxy-2,3,4,5-tetrahydrofuran-3-carboxamido] methyl}-3,4-dimethoxy-2,3,4,5-tetrahydrofuran-3-carboxylate', ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE, 66 O2699-U1584 (2010) [C1] 2010 Simone MI, Edwards AA, Cowley AR, Fleet GWJ, Watkin DJ, '(3R,4R,5R)-5-(Acetamidomethyl)-N-benzyl-3,4-dihydroxytetrahydrofuran-3-carboxamide', ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE, 66 O2750-U2003 (2010) [C1] 2009 Hobbs AJ, Gane P, Lumsden N, Nobles M, Rebstock A-S, Simone M, et al., 'Design and development of novel non-peptide agonists at natriuretic peptide receptor-C', FASEB JOURNAL, 23 (2009) [E3] 2008 Simone MI, Edwards AA, Tranter GE, Fleet GWJ, 'Carbon-branched delta-tetrahydrofuran sugar amino acids (SAAs) as dipeptide isostere scaffolds', TETRAHEDRON-ASYMMETRY, 19 2887-2894 (2008) [C1]