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. Much of our work has focused on the single flagellum of T. brucei that is critical for motility in different stages of the life cycle. While the eukaryotic flagellar structure is well defined, very little is known about regulation and control of motility, and recent evidence suggests that flagellar regulation in trypanosomes maybe very different than in organisms traditionally used for flagellar studies. To better understand the role of the flagellum in parasite biology, we have been characterizing proteins of the "inner arm dynein", a part of the flagellar axoneme. One of these genes is known as IC138, an intermediate chain of the I1/f dynein, it is required for flagellar motility and is a known dynein regulator; the other is DNAH10, encoding ons of the heavy chains of dynein I1/f. We use molecular genetics to knockdown or clone genes of interest, and then observe the effects of mutants on cell viability and flagellar function. We have also created strains that carry tags to these proteins so we can study where they localize in the cell using biochemical fractionation and microscopy, and purify the proteins for biochemical analyses. We also can engineer mutants of IC138 to alter its interactions with partner proteins and study the effect.
More recently 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. 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 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]