Buddy Ullman, PhD
Parasites - Molecular Parasitology – Purine Nucleoside/Nucleobase Transport - Purine and Pyrimidine Metabolism - Polyamine Transport and Biosynthesis
Amalgamating the tools of molecular biology, biochemistry, genetics, genomics, and structural biology, the Ullman laboratory investigates unique transport, metabolic, and organellar targeting pathways in protozoan parasites that might be amenable to therapeutic exploitation or vaccine development. Our laboratory primarily focuses on Leishmania donovani and Trypanosoma cruzi, the etiologic agents of visceral leishmaniasis and Chagas disease, respectively.
Current projects include the genetic and biochemical characterization of the purine, polyamine, and pyrimidine pathways of these parasites and the molecular genetic dissection of the adaptive responses of Leishmania to essential nutrient depletion. Generalized objectives of our research program include: (1) evaluation of gene function in intact parasites using targeted gene replacement strategies;(2) determination of biochemical characteristics and 3-dimensional structures of key proteins;(3) validation and exploitation of potential drug and vaccine targets;and (4) molecular analysis of the responses of Leishmania to purine starvation as a genetically tractable model to environmental stress.
Through the use of RNA-seq and proteomics, we have analyzed the complex, temporarily coordinated post-transcriptional responses that occur during purine starvation (these organisms do not regulate gene expression at the level of transcription). These changes include pronounced up-regulation of purine transporters and salvage enzymes and down-regulation of replication and translational machinery components. We are now identifying the molecular mechanisms underlying these adaptations, including defining the pertinent regulatory cis-acting sequences and identifying the trans-acting factors that bind to these sequences.