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Main Objective
The main scientific and technological objective of this
project is the development, assessment and application of tomographic and
microscopic technologies combined with novel fluorescent probes that will allow
in vivo imaging of important biological processes in subcellular, cellular,
organ, embryo and whole animal levels. To achieve this integrating and unifying
view we have combined multidisciplinary research and technology expertise in
Biology, Bioorganic Chemistry, Engineering, Theoretical Physics and Biomedical
Optics. These groups will be integrated both “vertically”, (experts in different
fields will work together on the same project), and “horizontally” (experts in
each field will work on a number of different projects).
Why
In-Vivo Molecular Imaging?
Advances in molecular biology have provided considerable
information concerning the sequence, structure and function of genes. This has
opened new perspectives for the understanding of fundamental biological
processes underlying human disease and for the development of innovative
diagnostic, prognostic and therapeutic tools. Strategies for genomic research
and therapeutic interventions at the genetic level will benefit from increased
capability to monitor in-vivo the effects of genetic manipulations in cells and
living organisms. Ironically, although biology is fundamentally dynamic, most of
the current knowledge on gene expression, regulation and delivery in mammalian
systems relies on results from in-vitro or ex-vivo studies. This, coupled with
our inability to easily monitor multiple molecular species simultaneously,
seriously limits our ability to study a wide range of biological processes.
Furthermore, since empirical descriptions of the evolution of systems over time
are generally constructed from series of data obtained from different specimens,
they often fail to accurately represent the true order of events. Additionally,
these invasive techniques tend to be time consuming and labor intensive, often
leading to distortion or even destruction of native properties. Thus the current
capacity to extract biological information in intact microenvironments of living
systems is severely limited. We believe that the ability to monitor the dynamics
of multiple molecules within living systems will transform our understanding of
biology, making experimental investigations much more efficient and accelerating
progress in the life sciences.
Project
Implementation
The
main scientific and technological objective of this project is the development,
assessment and application of tomographic and microscopic
technologies combined with novel fluorescent probes that will allow in
vivo imaging of important biological processes in subcellular, cellular,
organ, embryos and whole animals. To achieve this integrating and unifying view
we have combined multidisciplinary research and technology expertise in Biology,
Bioorganic Chemistry, Engineering, Theoretical Physics and Biomedical Optics.
To achieve our objectives in this area three main subprojects
have been devised; each one of them has been subdivided into workpackages that
address the instrumentation, theoretical developments and, finally, the
biological assessment of the techniques:
The Probe Development subproject contains workpackages and
tasks which are integral parts and utilized throughout the other two
subprojects.
The Animal and Cell imaging subprojects are organized in a
parallel way under the general areas of:
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High
throughput instrumentation technology. In each of those workpackages the
objective is to use existing and novel biotechnology tools (probes, cell and
animal models) to increase sensitivity, specificity and resolution of
existing and novel imaging devices. We will identify bottlenecks in in
vivo molecular imaging approaches and seek solutions using specifically
designed instrumentation and software.
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Theory development and basic experimental
assessment of the underlying physical principles. In these workpackages we
shall improve the modelling of the physical phenomena existing in each of
the proposed experimental set-ups. This will increase our understanding and
interpretation of the data acquired and boost the resolution,
sensitivity and specificity to the optimal achievable value.
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Biological applications. The improved and novel
technologies described above will be applied to address important biological
questions.The target biological systems have been chosen to cover a wide
range of biology fields, so that the consortium will be able to offer
technologies that can be used by as many as possible potential future users.
In order for this proposal to reach its goals, it is
imperative that interaction between the different disciplines is achieved
throughout its implementation. Instrument development requires constant
interaction with theoretical developers in order to overcome problems
encountered during the system’s set-up. In parallel, probe development will be
applied to test and quantify probe suitability in each imaging approach to
identify optimal probes and experimental configuration. This will be possible
through constant interaction between all the involved disciplines.
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