Monthly Seminar Program
Guest Speakers:
Dr. Jose Gutierrez Marcos
University of Warwick
Phd Speakers:
Arturas Grauslys
Alex Jironkin
Marcus Elze
February 8th , 2013
Seminar program
Time
13:00-14:00
Session
Lunch
Location
Common room
14:00-15:00
Invited guest speaker
MOAC Seminar room
15:00-15:15
Tea and coffee break
Common room
15:15-16:15
3 Phd Presentations
Phd presentations consist 15 minute talks (including questions) audience rotates between
three rooms
Speaker 1 Arturas Grauslys
Speaker 2 Alex Jironkin
Speaker 3 Marcus Elze
MOAC Seminar Room
WSB 32
WSB 336
16:15-16:20
Break
Common room
16:20-16:30
Evaluation of seminar series
A brief discussion on how the seminar series is
progressing, please send any issues to be raised
to Lesley.Foster@warwick.ac.uk
MOAC Seminar room
16:30 onwards
Wine and Cheese
Common room
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Presentation Description
Guest Speaker Session
Transgenerational Epigenetic Inheritance
Epigenetic modifications are widely accepted as playing a critical role in
the regulation of gene expression and thereby contributing to the determination of the phenotype of multicellular organisms. In general, these marks
are cleared and reestablished each generation, but there have been reports in
a number of model organisms that at some loci in the genome this clearing
is incomplete. This phenomenon is referred to as transgenerational epigenetic inheritance. My group is currently investigating how the environment
can stably influence the establishment of the epigenome. Our data suggest
that an environmental event in one generation could affect the phenotype in
subsequent generations, a Lamarckian idea that has been discarded for over
two centuries of genetic studies.
Phd Session 1:
Arturas Grauslys
Systems Pharmacology a strategy for antimalarial drug discovery
Malaria is a vastly spread mosquito-borne tropical disease and one of
the biggest killers in the world today. Multiple drugs are available for treatment of malaria, however increasing numbers of cases of drug resistance demand for alternative treatments. This project follows from recent black-box
screenings of compounds for potential effect against malaria causing parasite
P. falciparum. From over 20 000 compounds found to have such antimalarial
effect 400 were chosen as a representative set for further investigation. The
principal aim of the project is to develop Systems Pharmacology as a new
scientific discipline through integration of Medicinal Chemistry, Pharmacology and Mathematics. The challenge of antimalarial drug discovery will be
used as a pathfinder that can enhance our fundamental understanding of
parasite biology and deliver prioritized drug targets and drug leads. The
working hypothesis is that there are a finite number of drug targets and the
compounds in question will be used to affect these vulnerable points of the
parasite biochemistry. By using state of the art metabolomic fingerprinting
techniques and high content imaging coupled with mathematical analysis
we expect to develop a novel screening approach for antimalarial drugs in
order to discover new modes of action.
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Phd Session 2:
Alex Jironkin
When bacteria invade: a tale of mystery, detective work and science
A short talk on the advances in genomic sequencing and analyses in the
fight against MRSA.
Phd Session 3:
Marcus Elze
Modelling Survival following Bone Marrow Transplantation using
Longitudinal Immune Measurements at Arbitrary Time Points
Haematopoietic stem cell transplantation (bone marrow transplantation)
is a potentially curative treatment option for different hematologic and oncologic disorders, such as severe leukaemia. However, it is still associated with
high mortality rates due to complications after transplantation. Early identification of high-risk patients is crucial for successful intervention. Models
that predict patient survival or individual complication risks are needed to
assist clinical decision making and may provide insights into the underlying
biological processes.
The speed of immune recovery over time and several patient- and transplantationrelated covariates were shown to be associated with survival and complication risk. We investigate a dataset of 67 paediatric and young adult patients.
Approximately 2000 longitudinal measurements of several immunological
subpopulations were taken at arbitrary time points. Measurement time
points and frequency cannot be assumed to be independent of the survival
process.
Joint modelling of longitudinal and time-to-event data is a natural approach to data of this nature. Implementations of joint modelling techniques
in R and other languages are readily available. However, no consensus has
been reached yet on how to best assess goodness of fit and predictive ability
of such a model.
For exploratory analyses and for use in clinical practice simpler models
may be preferred. A simple comparison of measurements at a single time
point is sometimes found in biological publications. A cutoff value may
be used to group patients into high-risk and low-risk groups. However,
bias may be associated with such an approach. Bias can be reduced by
using appropriate summary measurements, such as the area under the curve,
and accelerated failure time models can be fitted. This has the advantage
that many measures of the prognostic ability of survival models are readily
available, e.g. explained variation. These simpler models may be used to
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specify a joint model and joint modelling may in turn inform the simpler
models.
A possible extension of joint modelling is the inclusion of a proportion
cured component to allow for the fact that patients may have a normal life
expectancy after a certain period of relapse-free survival. Furthermore, the
incorporation of the measurement frequency as a variable in the longitudinal
modelling may inform on the risk assessment by the clinicians.
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