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The interplay between cell cycle and metabolism in cancer cells
The interplay between cell cycle and metabolism in cancer cells
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The goal of this project is to investigate the molecular mechanisms that
synchronize cell cycle and cellular metabolism. For example, which
regulatory and metabolic genes participate in the activation of
nucleotide synthesis during DNA synthesis (S) phase of cell cycle? A
major assumption of the project is that new scientific insight can be
obtained by exploration of the voluminous corpus of scientific
literature describing in detail interactions between molecular
components of the cell. We believe that linking together articles
describing individual interactions of enzymes, transcription factors,
protein kinases etc. we will uncover molecular pathways not previously
The interplay between cell cycle and metabolism in cancer cells
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considered due to the volume and complexity of scientific literature.
The starting point of the project will be two classical computational
models already compiling large number of research articles. The model of
Calzone and collegues [1] compiles 350 research articles to provide a
detailed map of molecular interactions taking place in the regulation of
the cell cycle by the retinoblastoma protein (RB/RB1). The Recon2 model
[2, 3] is a recently updated representation of a complete set metabolic
reactions encoded by human genome. The model compiles evidence for about
7000 metabolic conversions in human cell.
The interplay between cell cycle and metabolism in cancer cells
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The student working on this project will for the first time integrate
these two literature-based computer models. We stress that this task
requires biological knowledge and interest rather than mathematical
modeling skills; all training in computer programs will be provided as
part of the research project. The student will search literature for
evidence of cell cycle control pathways regulating enzymes and add
connections to the model using well-established academic software with
graphical user interface [4, 5]. This will further extend the corpus of
research literature analysed for the first time together in a
computational model. Subsequently, the student will perform computer
simulations using algorithms already implemented in the software.
The interplay between cell cycle and metabolism in cancer cells
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Results will be presented in the formats similar to experimental data.
Thus, the student will effectively perform “in silico” rather than
laboratory experiments to identify novel pathways involved in
synchronization of cell cycle and metabolism during emergence of cancer.
This may lead to identification of potential vulnerabilities of cancer
cells that will inform future experimental research towards new
therapies and personalized, diagnostic methods.
