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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.