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Open Projects - Part III or PhD
DNA origami nanopores
Probing the force on DNA-protein complexes in a nanocapillary
Mimicking protein channels in a chip
All projects on this page can also be done as a summer project or expanded into
full PhD projects. Contact Ulrich Keyser by email for information, ufk20 (at)
cam.ac.uk. Detailed projects descriptions with the relevant, recent group
publications can be found below.
DNA origami nanopores
Nanopores are an emerging technique for the sensing of a variety of biomolecules such as DNA, RNA and proteins. Molecules are detected by measuring changes in ionic current as they translocate through a pore several tens of nanometres in size. An outstanding challenge in the field is the control of pore geometry and surface chemistry on the nanometre scale. In this project we will make nanopores by pulling glass capillaries with diameters down to 20 nm as recently demonstrated by our group. We will then experiment with functionalising the pore using DNA origami constructs to try to control the passage of other molecules through the pore. These ground-breaking experiments will allow for the design of functional nanopores with atomic level control of the surface properties.
You will learn:
Handling/making small nanopores
Single molecule measurements with nanopores
DNA origami technology
Data analysis and modeling
N. A. W. Bell, C. A. Engst, A. Ablay, G. Divitini, C. Ducati, T. Liedl, and
U. F. Keyser.
DNA origami nanopores.
Nano Letters (published online 20.12.2011), 2011.
[ DOI |
http ]
L. J. Steinbock, O. Otto, C. Chimerel, J. L. Gornall, and U. F. Keyser Detecting DNA
folding with nanocapillaries Nano Letters, 10, 2493 (2010)
Probing the force on DNA-protein complexes in a nanocapillary Recently, we
demonstrated for the first time the detection of the folding state of
double-stranded DNA in nanocapillaries with the resistive pulse technique. We show
that glass capillaries can be pulled into nanocapillaries with diameters down to 20
nm. We study translocation of DNA which is driven by an electrophoretic force
through the nanocapillary. We would like to push the limits of the technique by detecting
a single protein molecule on a DNA strand in a nanocapillary by combined measurements with
optical tweezers and nanocapillary-based resistive-pulse sensing.
You will learn:
Making small nanocapillaries
Single molecule measurements with nanocapillaries
Optical tweezers
Data analysis and modeling
L. J. Steinbock, O. Otto, D. R. Skarstam, S. Jahn, C. Chimerel, J. L. Gornall, and
U. F. Keyser Probing DNA with Micro- and
Nanocapillaries and Optical Tweezers Journal of Physics: Condensed
Matter, in press
L. J. Steinbock, O. Otto, C. Chimerel, J. L. Gornall, and U. F. Keyser Detecting DNA
folding with nanocapillaries Nano Letters, 10, 2493 (2010)
U. F. Keyser, S. van Dorp, and S. G. Lemay Tether forces in DNA electrophoresis Chemical Society
Reviews, 39, 939 (2010)
Mimicking protein channels in a chip
Transport of ions, metabolite molecules and macromolecular solutes across biological membranes is an ubiquitous process in nature. Specifically membrane proteins form metabolite-specific channels with large aqueous pores exhibiting affinities to their metabolites. Recently we have introduced a novel approach for the control, detection and manipulation of single nanoparticles by combining microfluidics with laser scattering and holographic optical tweezers. The aim of this project is to study the particle translocations through micro/nano-fluidic channels driven by concentration gradients or electro-osmotic/phoretic forces.
You will learn:
Fabrication of miniaturized lab-on-a-chip devices
Control of holographic optical tweezers for optical detection and manipulation
Programming LabVIEW routines for data analysis and device control
Theoretical modeling
A. M. Berezhkovskii and S. M. Bezrukov
Optimizing Transport of Metabolites through Large Channels: Molecular Sieves with and without Binding
Biophysical Journal, 88, L17 (2005)
S. Pagliara, C. Chimerel, D. G. A. L. Aarts, R. Langford and U. F. Keyser
Parallel sub-micrometer channels with different dimensions for laser scattering detection
Lab on a Chip, in press.
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