PhD: Princeton University, Molecular Biology
Postdoctoral training: California Institute of Technology, University of Washington
Cells are capable of so many precise and intricate functions that I never tire of learning about how biological processes work. In my research I bring together aspects of molecular genetics, microbiology and biochemistry to understand the biology of pathogenic protozoans, in particular the African trypanosome, Trypanosoma brucei that causes African sleeping sickness. New drug therapies against this parasite are badly needed and thus a better understanding of its biology is crucial.
Currently, my work is mainly focused on projects performed in the Biochem 426 course, we have begun studying the function of the three isoforms of malate dehydrogenase (MDH) in T. brucei. This NAD-dependent dehydrogenase has multiple roles in the cell, including in the citric acid cycle and in maintaining redox balance. The structure of many MDH proteins has been published, as well as details into quaternary formations and regulation. As a result, we can ask questions about minute details of how different amino acids affect catalysis. Furthermore, recent studies from other organisms suggest that some MDH isoforms form distinct interactions with other enzymes of the tricarboxylic acid (TCA) cycle, to promote high flux of intermediates via substrate channeling. We are interested in determining if any of the T. brucei MDH isoforms might share these properties. Our goals are to distinguish the biochemical properties of the different T. brucei isoforms in vitro, as well as to investigate localization and expression patterns in the cell. We have collaborators from other institutions working with malate dehydrogenases from many organisms, providing many areas for comparative studies of this important metabolic enzyme.
(* = undergraduate researcher)
Wilson, CS, Chang, AJ*, Greene, R*, Machado, S*, Parsons, MW*, Takats, TA*, Zambetti LJ*, Springer, AL. 2015. Characterization of TbIC138: a putative regulator of inner arm dynein in Trypanosoma. brucei. PLOS ONE. Publication date: Nov 10. 2015 [PubMed]
Jaswal, SS, O’Hara PB, Williamson PL, Springer, AL. 2013. Teaching structure: Student use of software tools for understanding macromolecular structure in an undergraduate biochemistry course. Biochemistry and Molecular Biology Education, 41: 351-359. [PubMed]
Zukas R*, Chang AJ*, Rice M, Springer, AL. 2012. Structural analysis of flagellar axonemes from inner arm dynein knockdown strains of Trypanosoma brucei. BioCell (formerly Electron Microscopy and Cell Biology), 36:133-142. [PubMed]
Springer, AL, Bruhn, DF, Kinzel KW*, Rosenthal NF*, Zukas R*, Klingbeil MM. 2011. Silencing of a putative inner arm dynein heavy chain results in flagellar immotility in Trypanosoma brucei. Mol Biochem Parasitol, 175:68-75. [PubMed]
Recker M, Serazin A, Kyes SA, Pinches R, Christodoulou Z, Springer AL, Gupta S, Newbold CI. 2011. Antigenic variation in malaria involves a highly structured switching pattern. PLOS Pathogens, 7:e1001306. [PubMed]
Howell DPG, Levin EA, Springer AL, Kraemer SK, Phippard DJ*, Fleischman SJ, Schief WR, Smith JD. 2008. Mapping a common interaction site is used by the P. falciparum Duffy binding-like (DBL) domain to bind diverse host receptors. Molecular Microbiology, 67:78-87 [PubMed]
Kraemer SM, Kyes SA, Aggarwal G, Springer AL, Nelson SO, Christodoulou Z, Smith LM, Wang W, Levin EA, Newbold CI, Myler, PJ, Smith, JD. 2007. Comparisons of var gene repertoires in Plasmodium falciparum support a unifying mechanism of evolution. BMC Genomics, 8:45. [PubMed]
Springer AL, Smith LM, Mackay DQ, Nelson SO, Smith JD. 2004. Functional interdependence of the DBLbeta domain and c2 region for binding of the Plasmodium falciparum variant antigen to ICAM-1. Mol Biochem Parasitol 137:55-64. [PubMed]