Honors & Awards
Stanford Graduate Fellowship, Stanford University (September 2013-August 2016)
Education & Certifications
Bachelor of Science, University of Massachusetts Amherst, Microbiology (2013)
Bachelor of Science, University of Massachusetts Amherst, Biochemistry & Molecular Biology (2013)
Integrative proteomics and bioinformatic prediction enable a high-confidence apicoplast proteome in malaria parasites.
2018; 16 (9): e2005895
Malaria parasites (Plasmodium spp.) and related apicomplexan pathogens contain a nonphotosynthetic plastid called the apicoplast. Derived from an unusual secondary eukaryote-eukaryote endosymbiosis, the apicoplast is a fascinating organelle whose function and biogenesis rely on a complex amalgamation of bacterial and algal pathways. Because these pathways are distinct from the human host, the apicoplast is an excellent source of novel antimalarial targets. Despite its biomedical importance and evolutionary significance, the absence of a reliable apicoplast proteome has limited most studies to the handful of pathways identified by homology to bacteria or primary chloroplasts, precluding our ability to study the most novel apicoplast pathways. Here, we combine proximity biotinylation-based proteomics (BioID) and a new machine learning algorithm to generate a high-confidence apicoplast proteome consisting of 346 proteins. Critically, the high accuracy of this proteome significantly outperforms previous prediction-based methods and extends beyond other BioID studies of unique parasite compartments. Half of identified proteins have unknown function, and 77% are predicted to be important for normal blood-stage growth. We validate the apicoplast localization of a subset of novel proteins and show that an ATP-binding cassette protein ABCF1 is essential for blood-stage survival and plays a previously unknown role in apicoplast biogenesis. These findings indicate critical organellar functions for newly discovered apicoplast proteins. The apicoplast proteome will be an important resource for elucidating unique pathways derived from secondary endosymbiosis and prioritizing antimalarial drug targets.
View details for DOI 10.1371/journal.pbio.2005895
View details for PubMedID 30212465
Cell cycle localization dynamics of mitochondrial DNA polymerase IC in African Trypanosomes.
Molecular biology of the cell
Trypanosoma brucei has a unique catenated mitochondrial DNA network called kinetoplast DNA (kDNA). Replication of kDNA occurs once per cell cycle in near synchrony with nuclear S phase and requires the coordination of numerous proteins. Among these are three essential DNA polymerases (TbPOLIB, IC, and ID). Localization dynamics of these proteins with respect to kDNA replication stages and how they coordinate their functions during replication are not well understood. We previously demonstrated that TbPOLID undergoes dynamic localization changes that are coupled to kDNA replication events. Here we report the localization of TbPOLIC, a second essential DNA polymerase, and demonstrate the accumulation of TbPOLIC foci at active kDNA replication sites (antipodal sites) during stage II of the kDNA duplication cycle. While TbPOLIC was undetectable by immunofluorescence during other cell cycle stages, steady state protein levels measured by western blot remained constant. TbPOLIC foci colocalized with the fraction of TbPOLID that localized to the antipodal sites. However, the partial co-localization of the two essential DNA polymerases suggests a highly dynamic environment at the antipodal sites to coordinate the trafficking of replication proteins during kDNA synthesis. These data indicate that cell cycle dependent localization is a major regulatory mechanism for essential mitochondrial DNA polymerases during kDNA replication. Video S1 Video S1 Supplementary Video 1.3D reconstruction of Stage IIa cell in Figure 3A. Video S2 Video S2 Supplementary Video 2.3D reconstruction of Stage IIb cell in Figure 3A - representing antipodal site localization. Video S3 Video S3 Supplementary Video 3.3D reconstruction of Stage IIb cell in Figure 3A - representing antipodal site and ULF zone localization. Video S4 Video S4 Supplementary Video 4.3D reconstruction of Stage IIb cell in Figure 3A - representing crescent shape localization associated with the KFZ/ULF zone.
View details for DOI 10.1091/mbc.E18-02-0127
View details for PubMedID 30133333