[c]
Registration: free for BSI members, 10 pounds for others.
To register, please email i2m  maths.leeds.ac.uk
Information
Programme
- 9:30-10:15
Mats Kvarnström (Fraunhofer-Chalmers, Sweden)
Quantitative image analysis in microscopy
The amount of recorded data from modern microscopes is huge and
seemingly constantly increasing. Furthermore, questions raised in
biology are getting more complex from bulk behavior of cells at a
specific time instant to single cell behavior and sometimes even
interaction between cells over time as the surrounding environment
changes. Due to the shear amount and complexity of data, quantitative
and automated methods are needed in order to carry out a thorough
analysis and to be able to draw viable conclusions from data.
In this talk I will present image analysis methods and algorithms for
recognition and tracking and subsequent extraction of data in
time-lapse light and fluorescence microscopy Examples will mainly be
drawn from yeast cell and hepatocyte bile canaliculi analysis but most
methods are generic in that the general methodology applies to a
variety of applications.
- 10:15-11:00
José Faro (University of Vigo, Spain)
How many selecting ligands are involved in thymocyte selection?
The TCR repertoire of a normal animal is shaped in the thymus by
ligand-specific positive- and negative-selection events. These processes are
believed to be determined at the single-cell level primarily by the affinity
of the TCR-ligand interactions. The relationships among all the variables
involved are still unknown due to the complexity of the interactions and the
lack of quantitative analysis of those parameters. We have developed a
quantitative model of thymic selection that provides estimates of the
fractions of positively and negatively selected thymocytes in the cortex and
in the medulla, as well as upper-bound ranges for the number of selecting
ligands required for the generation of a normal diverse TCR repertoire.
- 11:00-11:30 coffee
- 11:30-12:15
Mark Arnold (Veterinary Laboratories Agency)
Modelling the spread of H1N1 through the pig industry in Great Britain
The 2009 H1N1 swine influenza pandemic raised serious concerns about
the potential for pig-human transmission of the virus. While several
swine influenza viruses had become endemic in Great Britain (GB), the
potential for transmission of the pandemic 2009 H1N1 strain was very
uncertain and thus the potential for transmission from pigs to
agricultural workers was unknown. The objectives of this study were to
(i) explore the potential for transmission of 2009 pandemic H1N1 swine
influenza between pig holdings in GB and thus determine the likelihood
that this new strain of swine influenza would become endemic in the GB
pig population and (ii) provide estimates of the likely prevalence of
H1N1 swine influenza infected pig holdings over time, for input into a
human risk assessment. While the routes of transmission of swine
influenza between pig holdings was uncertain, it was expected that the
movement of infected pigs was the most likely route. Therefore a
network model of the pig industry was built, where the nodes of the
network were pig holdings and the links between holdings represented
the movements of infected pigs. Data on actual pig movements between
2002-2006 were obtained from official movement records, used in the
network model, which replayed the movements of pigs between pig
holdings from a random initial seed. This was coupled with a simple
model of within-holding transmission dynamics, to simulate the
within-holding prevalence. In addition to looking at the likely
holding-level prevalence, the model was also used to explore the
potential impact of vaccination on the propagation of H1N1 through the
pig industry.
- 12:15-13:30 lunch
- 13:30-14:15
Charlotte Cook (Veterinary Laboratories Agency)
Modelling the breeding for genetic resistance
to scrapie in the Cypriot goat population
Scrapie is a member of the family of transmissible spongiform
encephalopathy prion diseases that also include BSE in cattle and vCJD
in humans. Although no direct link to human vCJD has been proven
there remains concern that the disease may have impacts on human
health, particularly in goats. Due to this potential risk, disease
eradication measures are taken in scrapie-infected flocks of sheep and
goats. These actions involve the removal of animals that are
susceptible to the disease and encouraging breeding with animals that
are genetically resistant to clinical scrapie infection. Cyprus is
currently experiencing a large outbreak of scrapie in the sheep and
goat population. Whilst the genetics of resistance to scrapie in
sheep are well characterised and have been used as a disease
management tool for a number of years, the resistant genotypes within
goats have only recently been identified proposed. As part of the
actions for scrapie eradication and limitation in Cyprus, a breeding
for resistance program has been proposed. The aims of this project
were to simulate different breeding strategies and the impact of them
on the long-term goal of a wholly scrapie resistant goat population.
Data on the existing goat population structure was produced from a
government genetic resistance sampling programme. Currently of the
300,000 animals 100,000 have been testing for genetic resistance to
scrapie. A simulation model was built in R using Mendelian
inheritance patterns for resistance markers and artificial breeding
practices (AI). The model was used to investigate the effects of
difference selection techniques for breeding programs and selective
removal. The impact of different techniques is measured through the
proportion of scrapie resistance and susceptible animals in the
population, whilst maintaining desirable qualities such a goat breed
and age structure.
- 14:15-15:00
Alan Bennet (Adaptimmune, Oxford)
High affinity TCRs for T cell Adoptive Therapy of HIV and Cancer
Therapeutic cancer vaccination often produces good T cell responses but
this response generally fails to produce even a modest clinical benefit.
Adoptive T cell therapy where cancer-specific T cell receptors (TCRs) are
transfected into the patient's killer and helper T cells shows great
promise. Unfortunately, most cancer-specific T cells have a relatively low
avidity for target antigen and their ''wildtype'' TCRs are poorly-suited for
cancer therapy. At Adaptimmune and our sister company Immunocore we have
successfully used semi-randomly mutated TCR bacteriophage libraries to
isolate TCRs with greatly-enhanced antigen binding properties. I will
describe how mutant TCR bacteriophage libraries are generated and how
affinity-enhanced TCRs are identified by molecular evolution. The TCR
molecule is a heterodimer of two chains and high affinity mutants are found
in three main areas in each chain. These mutants can be combined to make
ultra-high affinity TCRs for antibody-like cancer cell targeting
(Immunocore) or can be partially back-mutated to produce more physiological
affinity-enhanced TCRs suitable for T cell adoptive therapy. The anti-
cancer cell activity of TCR-transfected T cell lines and the relationships
of target recognition and antigen specificities to TCR affinity and antigen
binding half-lives will be presented and discussed.
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