Professor Pauline Schaap
Cell and Developmental Biology, School of Life Sciences
+44 (0)1382 388078
Medical Sciences Institute
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 castellanii are exploited act as vectors for survival and airborne dispersal by bacterial pathogens, such as Legionella pneumoniae 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. 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. We recently found that Dictyostelia use c-di-GMP, an important prokaryote second messenger, as a secreted signal to induce stalk formation. c-di-GMP activates the adenylate cyclase ACA, which in turn activates PKA. ACA also produces the cAMP pulses that coordinate Dictyostelium aggregation and fruiting body formation, and is specifically expressed at the organizing tip. The interaction between c-di-GMP and ACA explained why the stalk is always formed from the tip.
We aim to establish how this and other PKA mediated pathways emerged from the ancestral encystation pathway as part of our overriding interest to understand how multicellular organisms evolved and acquired ever increasing levels of organisational complexity.
See figure 1 below: Signalling pathways that regulate encystation of solitary amoebas and multicellular development in Dictyostelium. Red text: Extracellular signals, blue text: intracellular signal proteins and small molecules; green text: enzymes that produce extracellular signals. Modified from: Schaap, 2016. Curr Opin Genet Dev. 39:29-34.
Experimental and evolutionary reconstruction of developmental signalling pathways
|Major Personal Funding Awards / ERC Advanced Grant||2017|
|Fellows of the Royal Society of Edinburgh||2013|
|Major Personal Funding Awards / Wellcome Trust Senior Investigator Award||2012|
|International Science Prizes awarded since 1990 / Correspondent Netherlands Royal Academy of Sciences||2011|
|Fellows of the Royal Society of Biology||2009|