Tuesday, 7 January 2014

Genomes and their value in Biotechnology

During the first part of the term all Y12 students were allocated a bacterial genome, following a number of lab sessions on how to use BLAST (Basic Local Alignment Search Tool) through the NCBI (National Center for Biotechnology Information). We first looked at the logic by which the BLAST algorithm compares a string of amino acids (in the form of the one-letter amino acid code) from one genome with another (BLASTP) and also at the DNA coding level (in the form of GAT or C). Remember that the searchable data sets are dynamic and that the computational methodology draws on a knowledge of protein chemistry and comparative sequence studies: it isn't quite like searching for a phone number: BLAST gives you not only a precise match, but also similar sequences (this isn't the case if you dial the wrong mobile number!)

In both cases, this powerful method rapidly enables a research worker to compare genes from different organisms and answer questions relating to biology (the evolutionary relationships between individual genes or whole genomes) and chemistry (the level of tolerance between the sequences of an enzyme or a gene regulatory molecule to mutation can give clues to the functional parts of a molecule). These are just two examples of how genomic data can help a research scientist. Indeed, it has been suggested by some influential scientists and commentators that experiments at the bench will become less common, as we learn to interpret genomic (and large data sets relating to proteomes and transcriptomes which are often called "omics"). 

I am not sure that Biology will become an in silico pursuit just yet, but it is certainly the case that as we accumulate knowledge of the components of cells and tissues and their interaction networks, the areas of Systems Biology and Synthetic Biology will become increasingly powerful and predictive. Wouldn't it be nice to be able to use Bioinformatics to design a new molecule or anew organism without spending time and money carrying out preliminary experiments? 

You should look at your allocated genome and ask the following questions.

Why was it sequenced? (Does it have a basis in medicine or some commercial interest beyond the basic Science value?) Are there any phenotypic features that make it interesting to compare with other organisms? Does it have any unique genes (or genes shared by a niche group)? Does it exhibit any epigenetic phenomena? 

Choose any pathway such as a metabolic pathway (the Krebs Cycle for example), or a regulatory pathway (gene activation or repression, for example the Trp operon), a biosynthetic process, such as protein synthesis, RNA synthesis, DNA synthesis, cell division or cell growth and map out the genes and proteins involved. Then compare these genes selectively with the rest of teh published genome data and try and place your organism into an evolutionary and functional context. If you want to make a start why not look at DNA replication, since all organisms have to do it and we looked at the DNA polymerases during the class. Recall, there are often several DNA polymerases found in prokaryotes, but some are useful but not essential. How similar are replication systems in prokaryotes and eukaryotes? In other word what difference if any doesa a nucleus make?

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