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Department of Chemical Engineering and Biotechnology

 

 

 

Shining Light on Neurodegeneration

Research summary

The Molecular Neuroscience Group focuses on investigating the molecular mechanisms that can cause neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer's disease (AD), and Huntington’s disease (HD).

Many neurodegenerative diseases are caused by aberrant forms of proteins which tend to accumulate and aggregate into shapes, which are believed to be toxic to the brain cells of affected patients. The proteins thought to cause disease are referred to as amyloid proteins. Amyloids are special in that, under circumstances not yet fully understood, they can ‘misfold’ and in the ensuing misfolded states they have a tendency to clump together, and be ‘trafficked’ from one neuron to another in the brains of patients suffering from diseases such as PD, AD, and HD. In order to study these processes in live cells/organisms we use primary neuronal cultures, neuronal cell lines, and small organisms such as the earthworm C. elegans as models of disease.

In the news

Congratulations to the authors of the recent paper "Structural progression of amyloid-β Arctic mutant aggregation in cells revealed by multi-parametric imaging.”! The paper was viewed 794 times on the JBC website in February and March, putting it among the top 50 most viewed papers for that time period. Read the paper and find more information here.

The review paper ” The Cellular Environment Affects Monomeric α-Synuclein Structure” is May's featured paper in Trends in Biochemical Sciences. Read the paper and find more information here.

Dr Colin Hockings' picture of neurons has been selected as a finalist for the Hughes Hall Postdoctoral Group inaugural Research Photography Exhibition. See more information and the finalist image in Outreach.

Dr Gabi Kaminski and along with other "scientists discover mechanism behind motor neurone disease". Read the article here or the full paper here.

Congratulations to Thea Zabel who was part of the winning Cambridge crew who beat Oxford to win the 73rd Women's Boat Race on the River Thames!

Dr Gabi Kaminski Schierle was interviewed by the Naked Scientists about how the "build up of Calcium could lead to Parkinson's". Read more here.

Researchers in the molecular neuroscience group have found that excess levels of calcium in brain cells may lead to the formation of toxic clusters that are the hallmark of Parkinson’s disease. Read more here.

Key words

Neurodegeneration, Alzheimer’s diseaseParkinson’s diseaseHuntington’s disease, amyloid protein, Tauα-synucleinHuntingtinprion-like propagationmicrofluidicsC. elegansintrinsic fluorescence of amyloid proteinsmulti-electrode arrays.

Our sponsors

MRCWellcome TrustAlzheimer's Research UK.

Key Publications

Lu M, Banetta L, Young LJ, Smith EJ, Bates GP, Zaccone A, Kaminski Schierle GS, Tunnacliffe A, Kaminski CF. “Live-cell super-resolution microscopy reveals a primary role for diffusion in polyglutamine-driven aggresome assembly” J Biol Chem, (2019), 294(1):257-268. doi: 10.1074/jbc.RA118.003500.

Stephens AD, Zacharopoulou M, Kaminski Schierle GS. ” The Cellular Environment Affects Monomeric α-Synuclein Structure” Trends Biochem Sci. (2018). pii: S0968-0004(18)30246-9. doi: 10.1016/j.tibs.2018.11.005. 

Lu M, Williamson N, Mishra A, Michel CH, Kaminski CF, Tunnacliffe A, Kaminski Schierle GS “Structural progression of amyloid-β Arctic mutant aggregation in cells revealed by multi-parametric imaging” J Biol Chem, (2018) Nov 30. doi: 10.1074/jbc.RA118.004511

 Stephens A D, Nespovitaya N, Zacharopoulou M, Kaminski C F, Phillips J J, Kaminski Schierle G S “Different Structural Conformers of Monomeric α-Synuclein Identified after Lyophilizing and Freezing” Analytical Chemistry, (2018), 90 (11), 6975-6983 doi:10.1021/acs.analchem.8b01264

Qamar S, Wang G, Randle S J, Simone Ruggeri F, Varela J A, Lin J Q, Phillips E C, Miyashita A, Williams D, Ströhl F, Meadows W, Ferry R, Dardov V J, Tartaglia G G, Farrer L A, Kaminski Schierle G S, Kaminski C F, Holt C E, Fraser P E, Schmitt-Ulms G, Klenerman D, Knowles T, Vendruscolo M, St George-Hyslop P, "FUS Phase Separation Is Modulated by a Molecular Chaperone and Methylation of Arginine Cation-π Interactions", Cell, (2018), 173, (3), 720-734.  doi.org/10.1016/j.cell.2018.03.056  | summary

Lautenschläger J, Stephens AD, Fusco G, Ströhl F, Curry N, Zacharopoulou M, Michel CH, Laine R, Nespovitaya N, Fantham M, Pinotsi D, Zago W, Fraser P, Tandon A, St George-Hyslop P, Rees E, Phillips JJ, De Simone A, Kaminski CF, Kaminski Schierle GS, "C-terminal calcium binding of α-synuclein modulates synaptic vesicle interaction", Nature Communications, (2018), 9 712.  doi:10.1038/s41467-018-03111-4  | summary

Lautenschläger J, Kaminski CF, Kaminski Schierle GS, "α-Synuclein – Regulator of Exocytosis, Endocytosis, or Both?", Trends in Cell Biology (2017).  doi:10.1016/j.tcb.2017.02.002

Pinotsi D, Michel CH, Buell AK, Laine RF, Mahou P, Dobson CM, Kaminski CF, Kaminski Schierle GS, "Nanoscopic insights into seeding mechanisms and toxicity of α-synuclein species in neurons" PNAS, (2016), 113 (14), 3815-3819. doi:10.1073/pnas.1516546113

Pinotsi D, Grisanti L, Mahou P, Gebauer R, Kaminski C, Hassanali A, Kaminski Schierle G,"Proton transfer and structure-specific fluorescence in hydrogen bond-rich protein structures", J. Am. Chem. Soc. (2016), 138 (9), 3046-3057. doi:10.1021/jacs.5b11012

Murakami T, Qamar S, Lin JQ, Kaminski Schierle GS, Rees E, Miyashita A, Costa AR, Dodd RB, Chan FTS, Michel CH, Kronenberg-Versteeg D, Li Y, Yang S-P, Wakutani Y, Meadows W, Ferry RR, Dong L, Tartaglia GG, Favrin G, Lin W-L, Dickson DW, Zhen M, Ron D, Schmitt-Ulms G, Fraser PE, Shneider NA, Holt C, Vendruscolo M, Kaminski CF, George-Hyslop P.St., "ALS/FTD mutation-induced phase transition of FUS liquid droplets and reversible hydrogels into irreversible hydrogels impairs RNP granule function", Neuron (2015). doi:10.1016/j.neuron.2015.10.030

Kaminski Schierle GS, van de Linde S, Erdelyi M, Esbjörner EK, Klein T, Rees E, Bertoncini CW, Dobson CM, Sauer M, and Kaminski CF, "In Situ Measurements of the Formation and Morphology of Intracellular ß-Amyloid Fibrils by Super-Resolution Fluorescence Imaging", J. Am. Chem. Soc., 133 (33), pp 12902–12905, (2011).  doi:10.1021/ja201651w

Complete list of publications