The use of Drosophila melanogaster to identify novel therapeutic agents for Alzheimer’s disease


   School of Life Sciences

  Dr M Georgiou, Dr Z Zhu  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Since 2003, our understanding of the causes of Alzheimer’s disease (AD) have improved considerably, however, in that time only one new drug treatment has been approved. The traditional animal of choice when modelling AD has been the mouse and although mouse models have proved to be invaluable, questions have been increasingly raised about the validity of using mouse models alone for AD drug discovery, particularly in light of the very high failure rate of clinical trials. We propose to use another AD model, the fruit fly, as an additional streamlining step in the drug development pipeline. This will, (1) address and improve the lack of translation between preclinical and clinical trials, and (2) lead to more informative and selective future mouse studies.

This project offers a PhD student the exciting opportunity to use the fruit fly (Drosophila melanogaster) as a model for AD, and to integrate sophisticated genetic and imaging techniques to identify novel drug treatments for this disease.

This project offers the student a fantastic opportunity to learn state-of-the-art techniques, including:

·      Sophisticated fly genetics

·      Live high-resolution imaging using confocal microscopy

·      Fly pupal mounting and dissections

·      Immunohistochemistry

·      Pre-clinical drug evaluation

·      Use of specialised imaging software

·      A wide variety of molecular biology techniques

·      Data analysis

·      Statistical analysis and numeracy skills

Biological Sciences (4) Medicine (26)

References

• URAS, G, MANCA, A, ZHANG, P, MARKUS, Z, MACK, N, ALLEN, S, BO, M, XU, S, XU, J, GEORGIOU, M and ZHU, Z, 2021. In vivo Evaluation of a Newly Synthesized Acetylcholinesterase Inhibitor in a Transgenic Drosophila Model of Alzheimer's Disease. Frontiers in neuroscience, 15, 691222
• CANALES COUTIÑO, B, SZAMEK, E, MARKUS, Z, and GEORGIOU, M, 2021. Generation and live imaging of tumors with specific genotypes in the living fly pupa. STAR Protocols, 2(3), 100672
• RUSU, A D, CORNHILL, Z E, CANALES COUTIÑO, B, CASTELLANOS URIBE, M, LOURDUSAMY, A, MARKUS, Z, MAY, S T, RAHMAN, R, and GEORGIOU, M, 2021. CG7379 and ING1 suppress cancer cell invasion by maintaining cell-cell junction integrity. Open biology, 11(9), 210077
• CANALES COUTIÑO, B, CORNHILL, Z E, COUTO, A, MACK, N A, RUSU, A D, NAGARAJAN, U, FAN, Y N, HADJICHARALAMBOUS, M R, CASTELLANOS URIBE, M, BURROWS, A, LOURDUSAMY, A, RAHMAN, R, MAY, S T, and GEORGIOU, M, 2020. A Genetic Analysis of Tumor Progression in Drosophila Identifies the Cohesin Complex as a Suppressor of Individual and Collective Cell Invasion. iScience, 23(6):101237.
• COUTO, A, MACK, N A, FAVIA, L and GEORGIOU, M, 2017. An apicobasal gradient of Rac activity determines protrusion form and position. Nature Communications, 8, 15385 doi: 10.1038/ncomms15385.
• Design, synthesis, biological evaluation, and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II), J Wang, C Wang, Z Wu, X Li, S Xu, J Liu, Q Lan, Z Zhu, J Xu, Chem Biol Drug Des 2018, 91(3):756-762.
• Multi-target design strategies for the improved treatment of Alzheimer's disease, P Zhang, S Xu, Z Zhu, J Xu, Eur J Med Chem 2019, 176:228-247.
• Design, synthesis and molecular modelling of isothiochromanone derivatives as acetylcholinesterase inhibitors, W Shuai, W Li, Y Yin, L Yang, F Xu, S Xu, H Yao, Z Zhu, J Xu, Future Med Chem 2019, 11(20):2687-2699.
• Design, Synthesis, and Biological Evaluation of Novel Chromanone Derivatives as Multifunctional Agents for the Treatment of Alzheimer's Disease, Xinnan Li, Tiantian Li, Feiyan Zhan, Feiyue Cheng, Li Lu, Bocheng Zhang, Junda Li, Zhaoxin Hu, Shengnan Zhou, Yilin Jia, Stephanie Allen, Lisa White, James Phillips, Zheying Zhu, Jinyi Xu, and Hequan Yao, ACS Chem. Neurosci. 2022, 13, 23, 3488–3501.
• New Insights into Neuroinflammation Involved in Pathogenic Mechanism of Alzheimer's Disease and Its Potential for Therapeutic Intervention, Li T, Lu L, Pember E, Li X, Zhang B, Zhu Z, Cells. 2022 11(12):1925. doi: 10.3390/cells11121925.
• Drosophila melanogaster as a model organism for Alzheimer’s disease. Prüßing, K. et. al. Mol Neurodegener. 2013; 8:35.

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