Dr Gabriele Kaminski Schierle

Interests

Our current research is focused on uncovering the molecular mechanisms that cause proteins to misfold and aggregate in live model systems of Alzheimer’s Disease (AD) and Parkinson’s disease (PD). To enable this work we have developed a range of advanced optical imaging techniques that permit us to look at these processes with unprecedented detail.

Two recent developments are key for this research:

1) Amyloids develop an intrinsic fluorescence that reports on the aggregation state of neurotoxic proteins

This discovery has permitted us to design highly specific and quantitative in vivo sensors of amyloidogenesis (see Kaminski Schierle et al., 2011)

2) direct Stochastic Optical Reconstruction Microscopy (dSTORM) quantifies the morphology of toxic species in cell models of disease

We were the first group able to visualise the morphology of aggregate species and their processing in situ in neuronal cells, at a resolution down to 10 nm (see Kaminski Schierle et al., 2011)

Strategy for an in vivo sensor of amyloid formation: In vivo sensing of amyloid nucleation and growth can be achieved by detecting fluorescence lifetime changes in extrinsic fluorophores acting as donors in a FRET like process, donating excitation energy to intrinsic energy states of amyloid structures. (Chan et al., 2013, in press).
Strategy for an in vivo sensor of amyloid formation: In vivo sensing of amyloid nucleation and growth can be achieved by detecting fluorescence lifetime changes in extrinsic fluorophores acting as donors in a FRET like process, donating excitation energy to intrinsic energy states of amyloid structures. (Chan et al., 2013, in press).
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Research Focus

Keywords

protein misfolding and aggregation

fluorescence lifetime imaging

superresolution microscopy

Clinical conditions

Alzheimer's disease

Parkinson's disease

Equipment

Calcium imaging

Cell culture

Confocal microscopy

Fluorescence Lifetime Imaging

Fluorescence microscopy

Immunohistochemistry

Polarisation resolved imaging

Spectral imaging

Superresolution Microscopy

Collaborators

Cambridge

Christopher Dobson

David Ron

Peter St. George Hyslop

International

Eckhard Mandelkow Web: http://www.dzne.de/en/site...

Associated News Items


Publications

2014

Chan FTS, Pinotsi D, Kaminski-Schierle GS, Kaminski CF (2014), “Structure-Specific Intrinsic Fluorescence of Protein Amyloids Used to Study their Kinetics of Aggregation” Bio-nanoimaging: Protein Misfolding & Aggregation, Academic Press pp. 147-155

Esbjörner EK, Chan F, Rees E, Erdelyi M, Luheshi LM, Bertoncini CW, Kaminski CF, Dobson CM, Kaminski Schierle GS (2014), “Direct Observations of Amyloid β Self-Assembly in Live Cells Provide Insights into Differences in the Kinetics of Aβ(1-40) and Aβ(1-42) Aggregation.” Chem Biol 21(6):732-42 Details

Kaminski CF, Rees EJ, Schierle GS (2014), “A quantitative protocol for intensity-based live cell FRET imaging.” Methods Mol Biol 1076:445-54 Details

Kaminski-Schierle GS, Sauer M, Kaminski CF (2014), “Probing Amyloid Aggregation and Morphology In Situ by Multiparameter Imaging and Super-Resolution Fluorescence Microscopy” Bio-nanoimaging: Protein Misfolding & Aggregation, Academic Press pp. 105-120

Michel CH, Kumar S, Pinotsi D, Tunnacliffe A, St George-Hyslop P, Mandelkow E, Mandelkow EM, Kaminski CF, Kaminski Schierle GS (2014), “Extracellular monomeric tau protein is sufficient to initiate the spread of tau protein pathology.” J Biol Chem 289(2):956-67 Details

Pinotsi D, Buell AK, Galvagnion C, Dobson CM, Kaminski Schierle GS, Kaminski CF (2014), “Direct observation of heterogeneous amyloid fibril growth kinetics via two-color super-resolution microscopy.” Nano Lett 14(1):339-45 Details

2013

Avezov E, Cross BC, Kaminski Schierle GS, Winters M, Harding HP, Melo EP, Kaminski CF, Ron D (2013), “Lifetime imaging of a fluorescent protein sensor reveals surprising stability of ER thiol redox.” J Cell Biol 201(2):337-49 Details

Chan FT, Kaminski Schierle GS, Kumita JR, Bertoncini CW, Dobson CM, Kaminski CF (2013), “Protein amyloids develop an intrinsic fluorescence signature during aggregation.” Analyst 138(7):2156-62 Details

Erdelyi M, Rees E, Metcalf D, Schierle GS, Dudas L, Sinko J, Knight AE, Kaminski CF (2013), “Correcting chromatic offset in multicolor super-resolution localization microscopy.” Opt Express 21(9):10978-88 Details

Erdelyi M, Rees EJ, Metcalf D, Kaminski-Schierle GS, Dudas L, Sinko J, Knight AE, Kaminski CF (2013), “Correcting chromatic offset in multicolor super-resolution localization microscopy” Optics Express 21 (9), 10978–10988

Pinotsi D, Buell AK, Dobson CM, Kaminski Schierle GS, Kaminski CF (2013), “A label-free, quantitative assay of amyloid fibril growth based on intrinsic fluorescence.” Chembiochem 14(7):846-50 Details

Pinotsi D, Kaminski-Schierle GS, Rees EJ, Kaminski CF (2013), “Localization microscopy for the study of amyloid fibril formation” Proc.SPIE 88150G 88150G (September 20, 2013)

Rees EJ, Erdelyi M, Kaminski-Schierle GS, Knight AE and Kaminski CF (2013), “Elements of image processing in localisation microscopy” Journal of Optics 15, 094012

2012

Ahn M, De Genst E, Kaminski Schierle GS, Erdelyi M, Kaminski CF, Dobson CM, Kumita JR (2012), “Analysis of the native structure, stability and aggregation of biotinylated human lysozyme.” PLoS One 7(11):e50192 Details

Chakrabortee S, Tripathi R, Watson M, Schierle GS, Kurniawan DP, Kaminski CF, Wise MJ, Tunnacliffe A (2012), “Intrinsically disordered proteins as molecular shields.” Mol Biosyst 8(1):210-9 Details

Murakami T, Yang SP, Xie L, Kawano T, Fu D, Mukai A, Bohm C, Chen F, Robertson J, Suzuki H, Tartaglia GG, Vendruscolo M, Kaminski Schierle GS, Chan FT, Moloney A, Crowther D, Kaminski CF, Zhen M, St George-Hyslop P (2012), “ALS mutations in FUS cause neuronal dysfunction and death in Caenorhabditis elegans by a dominant gain-of-function mechanism.” Hum Mol Genet 21(1):1-9 Details

2011

Chan FT, Kaminski CF, Kaminski Schierle GS (2011), “HomoFRET fluorescence anisotropy imaging as a tool to study molecular self-assembly in live cells.” Chemphyschem 12(3):500-9 Details

Esposito A, Bader AN, Schlachter SC, van den Heuvel DJ, Schierle GS, Venkitaraman AR, Kaminski CF, Gerritsen HC (2011), “Design and application of a confocal microscope for spectrally resolved anisotropy imaging.” Opt Express 19(3):2546-55 Details

Kaminski Schierle GS, Bertoncini CW, Chan FT, van der Goot AT, Schwedler S, Skepper J, Schlachter S, van Ham T, Esposito A, Kumita JR, Nollen EA, Dobson CM, Kaminski CF (2011), “A FRET sensor for non-invasive imaging of amyloid formation in vivo.” Chemphyschem 12(3):673-80 Details

Kaminski Schierle GS, van de Linde S, Erdelyi M, Esbjörner EK, Klein T, Rees E, Bertoncini CW, Dobson CM, Sauer M, Kaminski CF (2011), “In situ measurements of the formation and morphology of intracellular β-amyloid fibrils by super-resolution fluorescence imaging.” J Am Chem Soc 133(33):12902-5 Details

2010

Chakrabortee S, Meersman F, Kaminski Schierle GS, Bertoncini CW, McGee B, Kaminski CF, Tunnacliffe A (2010), “Catalytic and chaperone-like functions in an intrinsically disordered protein associated with desiccation tolerance.” Proc Natl Acad Sci U S A 107(37):16084-9 Details

van Ham TJ, Esposito A, Kumita JR, Hsu ST, Kaminski Schierle GS, Kaminski CF, Dobson CM, Nollen EA, Bertoncini CW (2010), “Towards multiparametric fluorescent imaging of amyloid formation: studies of a YFP model of alpha-synuclein aggregation.” J Mol Biol 395(3):627-42 Details

2009

Esposito A, Schlachter S, Schierle GS, Elder AD, Diaspro A, Wouters FS, Kaminski CF, Iliev AI (2009), “Quantitative fluorescence microscopy techniques.” Methods Mol Biol 586:117-42 Details

Schlachter S, Schwedler S, Esposito A, Kaminski Schierle GS, Moggridge GD, Kaminski CF (2009), “A method to unmix multiple fluorophores in microscopy images with minimal a priori information.” Opt Express 17(25):22747-60 Details

2005

Ahn YH, Bensadoun JC, Aebischer P, Zurn AD, Seiger A, Björklund A, Lindvall O, Wahlberg L, Brundin P, Kaminski Schierle GS (2005), “Increased fiber outgrowth from xeno-transplanted human embryonic dopaminergic neurons with co-implants of polymer-encapsulated genetically modified cells releasing glial cell line-derived neurotrophic factor.” Brain Res Bull 66(2):135-42 Details

2004

Boll JB, Geist MA, Kaminski Schierle GS, Petersen K, Leist M, Vaudano E (2004), “Improvement of embryonic dopaminergic neurone survival in culture and after grafting into the striatum of hemiparkinsonian rats by CEP-1347.” J Neurochem 88(3):698-707 Details

2003

Maciel EN, Kaminski Schierle GS, Hansson O, Brundin P, Castilho RF (2003), “Cyclosporin A and Bcl-2 do not inhibit quinolinic acid-induced striatal excitotoxicity in rodents.” Exp Neurol 183(2):430-7 Details

2000

Hansson O, Castilho RF, Kaminski Schierle GS, Karlsson J, Nicotera P, Leist M, Brundin P (2000), “Additive effects of caspase inhibitor and lazaroid on the survival of transplanted rat and human embryonic dopamine neurons.” Exp Neurol 164(1):102-11 Details

Mundt-Petersen U, Karlsson J, Schierle GS, Brundin P (2000), “Pretreatment with MK-801 or the lazaroid U-83836E does not enhance striatal graft survival.” Cell Transplant 9(1):73-8 Details

1999

Kaminski Schierle GS, Hansson O, Brundin P (1999), “Flunarizine improves the survival of grafted dopaminergic neurons.” Neuroscience 94(1):17-20 Details

Kaminski Schierle GS, Hansson O, Ferrando-May E, Nicotera P, Brundin P, Leist M (1999), “Neuronal death in nigral grafts in the absence of poly (ADP-ribose) polymerase activation.” Neuroreport 10(16):3347-51 Details

Schierle GS, Brundin P (1999), “Excitotoxicity plays a role in the death of tyrosine hydroxylase- immunopositive nigral neurons cultured in serum-free medium.” Exp Neurol 157(2):338-48 Details

Schierle GS, Hansson O, Leist M, Nicotera P, Widner H, Brundin P (1999), “Caspase inhibition reduces apoptosis and increases survival of nigral transplants.” Nat Med 5(1):97-100 Details

Schierle GS, Leist M, Martinou JC, Widner H, Nicotera P, Brundin P (1999), “Differential effects of Bcl-2 overexpression on fibre outgrowth and survival of embryonic dopaminergic neurons in intracerebral transplants.” Eur J Neurosci 11(9):3073-81 Details

1998

Schierle GS, Karlsson J, Brundin P (1998), “MK-801 does not enhance dopaminergic cell survival in embryonic nigral grafts.” Neuroreport 9(7):1313-6 Details

1997

Schierle GS, Gander JC, D'Orlando C, Ceilo MR, Vogt Weisenhorn DM (1997), “Calretinin-immunoreactivity during postnatal development of the rat isocortex: a qualitative and quantitative study.” Cereb Cortex 7(2):130-42 Details