Professor Pauline Schaap FRSE
Research
Most protozoa survive environmental stress by encapsulating to form a cyst or spore. This process is medically important because cysts of pathogenic protists are resistant to immune clearance, antibiotics and biocides. In addition, cysts of bacterivorous protists such as Acanthamoeba castellani are exploited act as vectors for survival and airborne dispersal by bacterial pathogens, such as Legionella pneumoniae, Vibrio cholerae and MRSA. Due to the limited genetic tractability of encysting organisms, the mechanisms controlling encystation are largely unknown. Dictyostelid social amoebas survive stress by building fruiting structures with encapsulated spores and stalk cells. Both cell types mature in response to cAMP activation of PKA. We showed earlier that this process is evolutionary derived from encystation in solitary amoebas, which we found to also require cAMP acting on PKA. The encysting Dictyostelid Polysphondylium pallidum is uniquely suitable for both reverse and forward genetic approaches, which allowed us to identify several encystation genes that proved to be deeply conserved in protozoa. This included one suitable target for anti-encystation drug development, which we are currently exploring in collaboration with the Dundee Drug Discovery Unit. In current research we combine the power of genetics with proteomic approaches to identify all genes that control encystation in P.pallidum. We also seek to identify missing links in the pathways that regulate spore and stalk cell encapsulation in Dictyostelia and to establish how these pathways emerged from the ancestral encystation pathway. This is part of our overriding interest to understand how multicellular organisms evolved and acquired ever increasing levels of organisational complexity. We seek to answer this question by combining comparative phenotypic analysis with comparative genomics and gene replacement in order to identify the genetic changes that caused phenotypic innovation.
Teaching
Two lectures and a problem solving tutorial in the 3rd Developmental Biology course.
Three hours of lectures in the 4th year module "Advanced topics in invertebrate development".
A guest lecture in the 3rd year Developmental Biology module at St Andrews University
A problem solving tutorial in the 4th year Numerical Scills module.
Supervision of two to three special study components for 1st year medical students
Supervision of a 4th year honours students and a summer student.
Publications
Kawabe, Y., Schilde, C., Du, Q., and Schaap, P. (2015). A conserved signalling pathway for amoebozoan encystation that was co-opted for multicellular development. Nature Scientific reports 5, 9644.
Schaap, P., Barrantes, I., Minx, P., Sasaki, N., Anderson, R. W., Benard, M., Biggar, K. K., Buchler, N. E., Bundschuh, R., Chen, X., et al. (2015). The Physarum polycephalum genome reveals extensive use of prokaryotic two-component and metazoan-type tyrosine kinase signaling. Genome Biol Evol. 8, 109-125.
Du, Q., Schilde, C., Birgersson, E., Chen, Z. H., McElroy, S., and Schaap, P. (2014). The cyclic AMP phosphodiesterase RegA critically regulates encystation in social and pathogenic amoebas. Cell Signal. 26, 453-459.
Schilde, C., Skiba, A., and Schaap, P. (2014). Evolutionary reconstruction of pattern formation in 98 Dictyostelium species reveals that cell-type specialization by lateral inhibition is a derived trait. EvoDevo 5, 34.
Romeralo, M., Skiba, A., Gonzalez-Voyer, A., Schilde, C., Lawal, H., Kedziora, S., Cavender, J. C., Glockner, G., Urushihara, H., and Schaap, P. (2013). Analysis of phenotypic evolution in Dictyostelia highlights developmental plasticity as a likely consequence of colonial multicellularity. Proc R. Soc. B. 280, 20130976.
Chen, Z-H and Schaap, P. (2012) The prokaryote messenger c-di-GMP triggers stalk cell differentiation in Dictyostelium. Nature 488, 680-683.
Kawabe, Y., Weening, K.E., Marquay-Markiewicz, J., and Schaap, P. (2012). Evolution of self-organisation in Dictyostelia by adaptation of a non-selective phosphodiesterase and a matrix component for regulated cAMP degradation. Development 139, 1336-1345.
Heidel, A., Lawal, H., Felder, M., Schilde, C., Helps, N., Tunggal, B., Rivero, F., John, U., Schleicher, M., Eichinger, L., Platzer, M., Noegel, A., Schaap, P* and Glockner, G*. (2011). Phylogeny-wide analysis of social amoeba genomes highlights ancient origins for complex intercellular communication. Genome research, 21, 1882-1891.* joint corresponding authors.
Schaap, P. (2011). Evolutionary crossroads in Developmental Biology: Dictyostelium discoideum Development 138, 387-396.
Kawabe, Y., Morio, T., James, J. L., Prescott, A. R., Tanaka, Y. and Schaap, P. (2009) Activated cAMP receptors turn encystation into sporulation. Proc. Nat. Acad. Sci. USA, 106, 7089-7094
Impact
Together with our collaborators, we have provided the research community with the first molecular phylogeny of most known species of Dictyostelia, and with three completely finished genomes which, with the D.discoideum genome, represent the four major groups of the Dictyostelid phylogeny. This information allows investigators to identify core components of any biological process studied in Dictyostelia and to retrace the evolutionary history of the process under study. This raises the characterization of a process from not only knowing its component parts, but to also understand why the process is built up the way it is.
Dictyostelium discoideum is already widely used to study fundamental processes related to human disease, but our research has opened new opportunities to use dictyostelids as genetically tractable models for understanding protist-borne disease. Most unicellular protists, including many pathogens, form resilient cysts when exposed to stress. By sequencing its genome and developing tools for molecular genetic analysis of the encysting dictyostelid Polysphondylium pallidum, we have established a genetically tractable model for studying amoebozoan encystation. This has already yielded one conserved potential drug target for inhibition of encystion of Acanthamoeba castellani, the causative agent of vision-destroying keratitis and lethal encephalitis.