Professor David Klenerman

University position

Professor

Professor David Klenerman is pleased to consider applications from prospective PhD students.

Departments

Department of Chemistry

Email

dk10012@cam.ac.uk

Home page

http://www.ch.cam.ac.uk/person/...

Research Theme

Cellular and Molecular Neuroscience

Interests

Small soluble protein aggregates are thought to play a key role in the initial development of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, but are difficult to study using conventional methods due to their low concentration and dynamic and heterogeneous nature. We have developed single molecule fluorescence based methods to detect and analyse the protein oligomers formed during an aggregation reaction, with time, and to study how these oligomers interact with the membrane of live neuronal cells and initiate and spread cellular damage.

Research Focus

Keywords

Single molecule fluorescence

beta amyloid

alpha synuclein

protein aggregation

Clinical conditions

Alzheimer's disease

Parkinson's disease

Equipment

Fluorescence microscopy

Collaborators

Cambridge

Chris Dobson

Tuomas Knowles

Peter St George-Hyslop

United Kingdom

Nick Wood Web: http://www.ucl.ac.uk/ukpdc/p...

Associated News Items


Publications

2014

Horrocks MH, Palayret M, Klenerman D, Lee SF (2014), “The changing point-spread function: single-molecule-based super-resolution imaging.” Histochem Cell Biol Details

2013

Clarke RW, Drews A, Browne H, Klenerman D (2013), “A single gD glycoprotein can mediate infection by Herpes simplex virus.” J Am Chem Soc 135(30):11175-80 Details

Clarke RW, Zhukov A, Richards O, Johnson N, Ostanin V, Klenerman D (2013), “Pipette-surface interaction: current enhancement and intrinsic force.” J Am Chem Soc 135(1):322-9 Details

Horrocks MH, Rajah L, Jönsson P, Kjaergaard M, Vendruscolo M, Knowles TP, Klenerman D (2013), “Single-molecule measurements of transient biomolecular complexes through microfluidic dilution.” Anal Chem 85(14):6855-9 Details

Klenerman D, Shevchuk A, Novak P, Korchev YE, Davis SJ (2013), “Imaging the cell surface and its organization down to the level of single molecules.” Philos Trans R Soc Lond B Biol Sci 368(1611):20120027 Details

Narayan P, Ganzinger KA, McColl J, Weimann L, Meehan S, Qamar S, Carver JA, Wilson MR, St George-Hyslop P, Dobson CM, Klenerman D (2013), “Single molecule characterization of the interactions between amyloid-β peptides and the membranes of hippocampal cells.” J Am Chem Soc 135(4):1491-8 Details

Shim JU, Ranasinghe RT, Smith CA, Ibrahim SM, Hollfelder F, Huck WT, Klenerman D, Abell C (2013), “Ultrarapid generation of femtoliter microfluidic droplets for single-molecule-counting immunoassays.” ACS Nano 7(7):5955-64 Details

Stephenson JD, Li H, Kenyon JC, Symmons M, Klenerman D, Lever AM (2013), “Three-dimensional RNA structure of the major HIV-1 packaging signal region.” Structure 21(6):951-62 Details

Weimann L, Ganzinger KA, McColl J, Irvine KL, Davis SJ, Gay NJ, Bryant CE, Klenerman D (2013), “A quantitative comparison of single-dye tracking analysis tools using Monte Carlo simulations.” PLoS One 8(5):e64287 Details

2012

Cremades N, Cohen SI, Deas E, Abramov AY, Chen AY, Orte A, Sandal M, Clarke RW, Dunne P, Aprile FA, Bertoncini CW, Wood NW, Knowles TP, Dobson CM, Klenerman D (2012), “Direct observation of the interconversion of normal and toxic forms of α-synuclein.” Cell 149(5):1048-59 Details

Horrocks MH, Li H, Shim JU, Ranasinghe RT, Clarke RW, Huck WT, Abell C, Klenerman D (2012), “Single molecule fluorescence under conditions of fast flow.” Anal Chem 84(1):179-85 Details

Jönsson P, McColl J, Clarke RW, Ostanin VP, Jönsson B, Klenerman D (2012), “Hydrodynamic trapping of molecules in lipid bilayers.” Proc Natl Acad Sci U S A 109(26):10328-33 Details

Lando D, Endesfelder U, Berger H, Subramanian L, Dunne PD, McColl J, Klenerman D, Carr AM, Sauer M, Allshire RC, Heilemann M, Laue ED (2012), “Quantitative single-molecule microscopy reveals that CENP-A(Cnp1) deposition occurs during G2 in fission yeast.” Open Biol 2(7):120078 Details

Narayan P, Meehan S, Carver JA, Wilson MR, Dobson CM, Klenerman D (2012), “Amyloid-β oligomers are sequestered by both intracellular and extracellular chaperones.” Biochemistry 51(46):9270-6 Details

Ye Y, Blaser G, Horrocks MH, Ruedas-Rama MJ, Ibrahim S, Zhukov AA, Orte A, Klenerman D, Jackson SE, Komander D (2012), “Ubiquitin chain conformation regulates recognition and activity of interacting proteins.” Nature 492(7428):266-70 Details

Zhukov A, Richards O, Ostanin V, Korchev Y, Klenerman D (2012), “A hybrid scanning mode for fast scanning ion conductance microscopy (SICM) imaging.” Ultramicroscopy 121:1-7 Details

2011

Klenerman D, Korchev YE, Davis SJ (2011), “Imaging and characterisation of the surface of live cells.” Curr Opin Chem Biol 15(5):696-703 Details

Narayan P, Orte A, Clarke RW, Bolognesi B, Hook S, Ganzinger KA, Meehan S, Wilson MR, Dobson CM, Klenerman D (2011), “The extracellular chaperone clusterin sequesters oligomeric forms of the amyloid-β(1-40) peptide.” Nat Struct Mol Biol 19(1):79-83 Details

2010

Bruckbauer A, Dunne PD, James P, Howes E, Zhou D, Jones R, Klenerman D (2010), “Selective diffusion barriers separate membrane compartments.” Biophys J 99(1):L1-3 Details

Jones R, Howes E, Dunne PD, James P, Bruckbauer A, Klenerman D (2010), “Tracking diffusion of GM1 gangliosides and zona pellucida binding molecules in sperm plasma membranes following cholesterol efflux.” Dev Biol 339(2):398-406 Details

Yeoman JA, Orte A, Ashbridge B, Klenerman D, Balasubramanian S (2010), “RNA conformation in catalytically active human telomerase.” J Am Chem Soc 132(9):2852-3 Details

2009

Ashbridge B, Orte A, Yeoman JA, Kirwan M, Vulliamy T, Dokal I, Klenerman D, Balasubramanian S (2009), “Single-molecule analysis of the human telomerase RNA.dyskerin interaction and the effect of dyskeratosis congenita mutations.” Biochemistry 48(46):10858-65 Details

Chiou A, Hägglöf P, Orte A, Chen AY, Dunne PD, Belorgey D, Karlsson-Li S, Lomas DA, Klenerman D (2009), “Probing neuroserpin polymerization and interaction with amyloid-beta peptides using single molecule fluorescence.” Biophys J 97(8):2306-15 Details

Shivji MK, Mukund SR, Rajendra E, Chen S, Short JM, Savill J, Klenerman D, Venkitaraman AR (2009), “The BRC repeats of human BRCA2 differentially regulate RAD51 binding on single- versus double-stranded DNA to stimulate strand exchange.” Proc Natl Acad Sci U S A 106(32):13254-9 Details

2008

Alves D, Li H, Codrington R, Orte A, Ren X, Klenerman D, Balasubramanian S (2008), “Single-molecule analysis of human telomerase monomer.” Nat Chem Biol 4(5):287-9 Details

Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J, Brown CG, Hall KP, Evers DJ, Barnes CL, Bignell HR, Boutell JM, Bryant J, Carter RJ, Keira Cheetham R, Cox AJ, Ellis DJ, Flatbush MR, Gormley NA, Humphray SJ, Irving LJ, Karbelashvili MS, Kirk SM, Li H, Liu X, Maisinger KS, Murray LJ, Obradovic B, Ost T, Parkinson ML, Pratt MR, Rasolonjatovo IM, Reed MT, Rigatti R, Rodighiero C, Ross MT, Sabot A, Sankar SV, Scally A, Schroth GP, Smith ME, Smith VP, Spiridou A, Torrance PE, Tzonev SS, Vermaas EH, Walter K, Wu X, Zhang L, Alam MD, Anastasi C, Aniebo IC, Bailey DM, Bancarz IR, Banerjee S, Barbour SG, Baybayan PA, Benoit VA, Benson KF, Bevis C, Black PJ, Boodhun A, Brennan JS, Bridgham JA, Brown RC, Brown AA, Buermann DH, Bundu AA, Burrows JC, Carter NP, Castillo N, Chiara E Catenazzi M, Chang S, Neil Cooley R, Crake NR, Dada OO, Diakoumakos KD, Dominguez-Fernandez B, Earnshaw DJ, Egbujor UC, Elmore DW, Etchin SS, Ewan MR, Fedurco M, Fraser LJ, Fuentes Fajardo KV, Scott Furey W, George D, Gietzen KJ (2008), “Accurate whole human genome sequencing using reversible terminator chemistry.” Nature 456(7218):53-9 Details

Orte A, Birkett NR, Clarke RW, Devlin GL, Dobson CM, Klenerman D (2008), “Direct characterization of amyloidogenic oligomers by single-molecule fluorescence.” Proc Natl Acad Sci U S A 105(38):14424-9 Details

Orte A, Clarke RW, Klenerman D (2008), “Fluorescence coincidence spectroscopy for single-molecule fluorescence resonance energy-transfer measurements.” Anal Chem 80(22):8389-97 Details

Orte A, Craggs TD, White SS, Jackson SE, Klenerman D (2008), “Evidence of an intermediate and parallel pathways in protein unfolding from single-molecule fluorescence.” J Am Chem Soc 130(25):7898-907 Details

Piper JD, Li C, Lo CJ, Berry R, Korchev Y, Ying L, Klenerman D (2008), “Characterization and application of controllable local chemical changes produced by reagent delivery from a nanopipet.” J Am Chem Soc 130(31):10386-93 Details