| Presenter |
Abstract/Interest |
Jun Allard
Grad student
Applied Math
UBC |
Models of the actin-like MreB helix in prokaryotes
MreB is an actin-like protein that
forms a helix running the length of cylindrical bacterial cells. I
present a model of the helix. Individual polymers making up the cables
are represented by simple force-dependent polymer models bundled into a
supramolecular array. Boundary conditions and external forces are
provided by a global elasticity model representing the cables as flexible
rods buckled into a helix inside the confinement of the cell wall. The
model produces relationships between pitch of the helix, cable thickness
and total abundance of MreB, and has implications for cell growth,
macromolecule trafficking and the polarization of Caulobacter.
|
Tom Depew
Grad student
Physics
UBC |
NMR investigation of structural biopolymers
Since its advent, Nuclear Magnetic Resonance (NMR) has aided the study of biological systems.
Mechanical and structural properties of proteins and polypeptides can be illuminated often by simple
NMR experiments. Our study has aimed to uncover characteristics of two different biomaterials that
show promise as replacement for synthetic materials.
Hagfish slime threads are a strong and elastic material composed of proteins forming intermediate
filament structures. We have studied the mobility of different regions of the protein and analysed the
effects of temperature on these properties. Experiments have shown features of both mobility and
structural rigidity in the backbone, suggesting regions which lend mechanical stiffness and others
that provide elastic flexibity.
Arthropods possess a rubber-like elastic energy storing material which provides the basis for
locomotive and other functions. The most notable feature of this material is its incredible resilience;
able to maintain structure and potential energy storing capabilities after many cycles. The NMR
spectrum has been analysed to identify amino acid content and conformational properties of 2
recombinant forms of the polypeptide. Relaxation experiments suggest a randomly structured,
highly mobile protein.
|
Omer Dushek
Grad student
Mathematics
UBC |
Analysis of serial engagement and peptide-MHC transport in T cell
receptor microclusters
During stimulation of a T cell by an antigen-presenting-cell (APC) bearing
cognate peptide-major-histocompatibility complexes (pMHC), T cell receptors
(TCR) have been shown to form stable micrometer-scale clusters in the
contact region. pMHC molecules diffusing in the APC membrane may bind and
unbind from multiple TCR in a cluster. We use mathematical modeling to
characterize the number of clustered TCR bound by a single pMHC. We show
that the TCR-pMHC bond kinetics alone do not allow substantial serial
engagement of TCR. Mathematical tools: MFP calculations, asymptotic
analysis, numerical solutions of PDEs.
|
Nahid Jetha
Grad student
Physics
UBC |
Single molecule force spectroscopy using nanopores provides an excellent means to probe the energy
landscapes associated with structural transitions in Prion protein
conversion (PrPC to PrPSC) taking place in Prion diseases such as
Creutzfeldt-Jakob disease. The technique is based on electrophoretically
driving a single Prion protein (immersed in an ionic solution) into a
nanometer-scale pore, and observing the modulation of ionic current
through the pore as structural domains fold and unfold due to the applied
electrostatic force. We present preliminary results, showing voltage
dependent structural transitions, which we associate with the melting and
annealing of the beta-sheet adjacent to the unstructured N-terminus
of PrPC. By measuring the rate of folding & unfolding over a range of
applied forces and temperatures the energy landscape associated with
these structural transitions can be reconstructed according to a modified Arrhenius relationship.
|
Joel Pel
Grad student
Physics
UBC |
A SCODA-based Instrument for Nucleic Acid Extraction from Challenging
Samples
Joel Pel, David Broemeling, Peter Eugster, Dylan Gunn, Laura Mail, Gareth
Mercerl, Jason Thompson, Andre Marziali
We have developed a novel electrophoretic technology that enables highly
efficient purification of nucleic acids from challenging samples. This
technology uses SCODA (Synchronous Coefficient of Drag Alteration), a novel
form of two-dimensional nonlinear electrophoresis, to recover DNA from
zeptomolar concentrations, and to recover fragments up to 1Mb in length
without shearing, as no centrifugation, filtration, or fluid-flow are
necessary. Time-varying electric fields are applied to the concentration
medium such that the highly nonlinear electrophoretic response of nucleic
acids causes them to move towards a common focus location. Since this
method acts only on molecules with highly nonlinear electrophoretic
behaviour, it preferentially concentrates nucleic acids over other
molecules.
|
Nadine Wicks
Grad student
Molecular Biology and biochemistry
SFU |
Mutation in the Voltage-Sensing Helix of HCN4 Channels Enhances cAMP-Dependent Stabilization of a Secondary Open State.
Pacemaker (HCN) channels are hyperpolarization-activated and their activity is enhanced by cAMP, but whether cAMP-gating is coupled to voltage-gating remains unresolved. With sufficiently long hyperpolarizations, HCN channels form a secondary open state; this briefly sustains activation after a return to resting voltages. cAMP effects on the secondary open state remain unclear. We studied HCN4 channels in excised membrane patches and found cAMP increases sustained activation. We also studied a charge-reversing S4 mutation (K381E) and found it causes surprisingly little change in voltage-dependence. Notably, K381E dramatically increases the cAMP-dependence of sustained activation. Our results suggest cAMP and K381E synergistically enhance the formation of a secondary open state; this indicates a physical coupling of voltage- and cAMP-sensing machinery in HCN channels.
|
Scott Cheng-Hsin Yang
Grad student
Physics
SFU |
DNA synthesis in Xenopus frog embryos
initiates stochastically in time at many sites (origins) along the
chromosome. Stochastic initiation implies fluctuations in the replication
time and may lead to cell death if replication takes longer than the cell
cycle time (~ 25 min.). Surprisingly, although the typical replication
time is about 20 min., in vivo experiments show that replication fails to
complete only about 1 in 250 times. How is replication timing accurately
controlled despite the stochasticity? We model DNA replication as a
nucleation-and-growth process and discuss possible mechanisms to control
replication time for both randomly and periodically placed origins.
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