|DECODING: large scale approaches to unravel genome decoding rules|
Programme - PTDC/BIA-GEN/110383/2009
Execution dates - 2011-01-01 - 2013-12-31 (36 Months)
Funding Entity - FCT
Funding for CESAM - 193.452 €
Total Funding - 193.452 €
Proponent Institution - Universidade de Aveiro
Gene evolution is modulated by a wide range of factors upon which natural selection operates. Some of these factors are associated with genome replication biases and errors, others are linked with DNA repair and recombination processes while others are associated with gene regulation, nucleic acid stability, modification and editing. Transcriptional and translational biases, mRNA maturation and regulatory processes also restrict gene evolutionary processes. We are interested in understanding how mRNA translation fidelity influences the evolution of open reading frames (ORFs) and we are motivated by a number of recent discoveries showing that protein synthesis fidelity has implications for gene evolution, cell homeostasis, human diseases and is also relevant for synthetic biology.
In this project we will integrate large scale comparative genomics, molecular biology, DNA microarray and bioinformatics methodologies to unravel how codon-context, codon-usage, tRNA abundance, tRNA modification, codon-anticodon pairing rules and environmental cues affect the fidelity of mRNA translation. For this, we will use sophisticated software tools developed by our bioinformatics group and will implement new tools for gene primary structure analysis and de novo gene design. Ab initio gene synthesis methodologies used in synthetic biology will be used to construct reporter genes for in vivo validation of the in silico data. Large scale simulations will be carried out to determine how the above mentioned gene primary structure variables influence gene evolutionary rates. One is expecting that these innovative approaches will define for the first time how mRNA translation shapes gene evolution and will allow us to develop new tools for de novo and ab initio gene design and construction which will have applications in the emerging field of synthetic biology.