| Popis: |
Millions die every year from infectious diseases such as tuberculosis, malaria and AIDS. More research needs to be performed to find new target sites (exotic DNA) for treatments of these pathologies. The majority of DNA is right-handed double-stranded (ds-) B-DNA. However, other forms of nucleic acids exist, viz., ds-Z-DNA, triple-stranded DNA and four-stranded DNA. Our group has developed novel ds-DNA microarrays that contain tuberculosis genes (Mycobacterium tuberculosis) and malaria genes [i.e., Plasmodium falciparum (var, rif and stevor genes)]. Employing the novel microarrays allows for the entire genes or segments to be immobilized as intact, unaltered, nondenatured DNA molecules. These microarrays allow for the discovery of drugs that bind to the immobilized intact genes under different environmental conditions (with or without proteins, supercoiling, ionic conditions, drugs). They also allow characterization of DNA structure and function. Using the new microarrays and bioinformatics, genes can be characterized for the presence of B-DNA and Z-DNA (transcription studies). Genes that contain DNA with the potential for B-DNA to Z-DNA transitions can be studied under specific environmental conditions. These infectious disease-based microarrays will include ds-Z-DNA, ds-B-DNA, B-DNA/Z-DNA junctions, mitochondrial DNA, and helical transitional arrays (B-DNA to Z-DNA). These new microarrays will allow for unprecedented drug discovery and gene expression studies. They will go beyond the limitations of commercially available, conventional ss-DNA microarrays (hybridization), which only focus on DNA primary structure (base pairs) and ignore DNA secondary structure. With these new microarrays, researchers will have access to all of the previously unexplored DNA structures that regulate gene expression. |
