BioSF Presentation by Joe DeRisi, PhD

Last night’s BioScience Forum presentation by Joe DeRisi PhD was about his lab‘s work using DNA microarrays to study two areas of research: elucidation of biochemical and transcriptional pathways of the malaria pathogen Plasmodium falciparum, and viral pathogen discovery. In both areas, the research involves chips spotted with 70-mer oligos. In the P. falciparum research, the 70-mer arrays allow the lab’s researchers to target the most unique regions of genes and provide the hybridization sensitivity needed to study the AT-rich genome of P. falciparum. In the viral pathogen research, the 70-mers enable detection of imperfectly matched conserved viral genome sequences.

Data from the P. falciparum research have disclosed that a highly canonical transcription schedule drives the organism’s 48-hour life cycle. Dr. DeRisi compared the P. falciparum life cycle to a JIT factory; the components of cell functions are produced only immediately prior to their use and not at other times. Dr. DeRisi pointed out that this feature may prove to be the pathogen’s Achilles’ heel. In the lab, any perturbation in bioreactor conditions results in "catastrophic failure" of a P. falciparum culture, as the organism does not have any of the machinery on hand needed to recover, or do anything other than what normally would occur next in its life cycle.

The viral pathogen discovery data Dr. DeRisi showed us was formed by hybridizing DNA from infected tissues with a comprehensive array of conserved viral sequences from the NCBI database. In addition to enabling discovery and preliminary characterization of previously unknown viruses, the approach also can match viral DNA from infected tissues with known viruses. In one case, an investigator using the approach discovered that for years he had been passing cultures infected by the foot-and-mouth disease virus. Upon being informed, the CDC arrived and neutralized the previously unsuspected biohazard.

Ben Borson JD PhD, BioScience Forum’s President, started the presentation ahead of schedule to allow Dr. DeRisi to finish early and get back to grant writing.