Genome Sequencing

Genome Sequencing

In recent years whole genomes of various organisms have been sequenced and sequencing of all sorts of organisms is going on all over the world. Such projects started with sequencing the genome of microorgan-isms, various prokaryotes as well as eukaryotes, but was extended to higher organisms like the nematode Caenorhabditis elegans, the insect Drosophila melanogaster,the plant Arabidopsis thaliana and finally, considered as the most prominent achievement in this respect, the genome of man, Homo sapiens.

The detailed knowledge of genome structures (“genomics”) has a great impact on biotechnology, not in the least on pharmaceutical biotechnology. However, knowing the genome sequence is only astart. But, it enables researchers to approach in a direct way functional aspects of the genome: when and how genes are expressed, in what way genes cooperate during their expression which enables us to under-stand gene networks, etc. Such an integrative genetic approach is generally called “functional genomics.” Functional genomics together with the detailed studies on the proteins that the cell produces (called “proteomics”) will give pharmaceutical biotechnology a new outlook.

As an example, the new future for pharmaceu-tical biotechnology can be illustrated by the develop-ment of new antibiotics. Classical antibiotics are isolated from nature as secondary metabolites pro-duced by various microorganisms. Their antibiotic properties are based on the interference with vital processes in pathogenic microorganisms. The number of target molecules in the bacterial cells which are affected by the classical antibiotics are rather limited (Note the different meaning of “target” in this context as compared to “drug targeting” discussed) For example, Mycobacterium tuberculosis causes tuberculosis, a disease with a great impact in the world. Detailed knowledge of the genome structure of pathogenic bacteria might reveal all kinds of specific vital target molecules in this pathogen. Detailed knowledge of new target molecules will enable the pharmaceutical scientist to synthesize chemical com-pounds which interfere with (the products of) vital target genes. The problem of the prevalence of pathogenic microorganisms resistant to classical antibiotics is now in principle open for a solution by synthesizing new target-directed chemical compounds.

Moreover, the human genome knowledge is the basis for recognition of all kinds of genetic poly-morphisms that distinguish individual people. In the near future, insight in the individual genes of a patient opens ways for more effective therapies based on a patient’s individual characteristics and needs. This emerging field in the pharmaceutical sciences with direct implications for the practitioner is called “pharmacogenetics.”

The pharmaceutical industry is highly interested in the possibilities arising from more detailed genome knowledge and is investing in functional genomics, proteomics and pharmacogenetics. The technological background and implications of func-tional genomics, proteomics and pharmacogenetics will be discussed in more detail.