Investigating transcriptional regulation of Plasmodium falciparum upon drug perturbation

Excerpt

Gene regulation of the malaria parasite Plasmodium falciparum has proven to be complex with evidence supporting both transcriptional [1, 2] and post-transcriptional level control [3, 4]. Transcriptional profiling of environmentally perturbed malaria parasites can reveal functionally related genes with common regulatory mechanisms that are responsive to external stimuli [2]. By interrogating microarray data derived from P. falciparum populations treated with several drug classes, a subset of four genes potentially involved with the parasite's survival mechanisms following drug perturbation were identified, i.e. general stress response genes. In addition, data from two independent functional genomics investigations on the response of P. falciparum parasites to polyamine biosynthesis inhibitors (DFMO/MDL73811 co-inhibition [5] and cyclohexylamine [6]), revealed four genes of which the transcript abundance appear to be uniquely affected upon polyamine depletion only [5, 6], i.e. perturbation-specific stress response genes. The regulation of this generalized versus perturbation-specific transcriptional responses was subsequently investigated. …