Co-option of cilia proteins in gene regulatory processes
1 PhD project proposal in the IPP summer call 2019
The eukaryotic cilium arose very early in the evolution of eukaryotes and has diversified to serve a wide range of sensory, motility and cellular signalling functions. The cilium is anchored to the cell via the basal body, corresponding to the centrosome in non-ciliated cells. It is now increasingly apparent that cilia-associated proteins also exhibit non-ciliary functions, including gene regulation, which likely evolved through a process of co-option. Evolutionary analysis has shown that basal body function is ancestral, whereas the presence of the centrosome is specific to the Holozoa. This indicates that in some taxa, such as Chlamydomonas and Trypanosoma although the organisms have a cilium, they lack a centrosome. We hypothesise that if the Holozoan centrosome is derived from the cilia’s basal body, the evolution of a gene regulatory function of basal body proteins coincided with the ‘new’ centrosomal function. In particular, the highly conserved Bardet-Biedl Syndrome (BBS) proteins that regulate microtubule-based ciliary trafficking have been linked to transcriptional regulation.
PhD project proposal: Co-option of cilia proteins in gene regulatory processes
To test the hypothesis that the evolution of gene regulatory functions arose with the emergence of a true centrosome, this PhD project will investigate ciliated organisms that either have or lack a ‘centrosome’ to determine whether possible gene regulation by ‘cilia’/BBS’ proteins co-evolved with the centrosome. Using bioinformatic approaches, we will systematically categorize cilia gene duplications, gene loss and alternative isoforms as well as the presence/absence of nuclear localization (NLS) and nuclear export (NES) sequences across various taxa. We will identify the cellular localization of ciliary proteins in various cultured model organisms (cell lines from Homo and Mus, Caenorhabditis, Chlamydomonas, Trypanosoma), via immunohistochemistry, gene modification approaches (endogenous tagging via CRISPR, transfection or transformation of tagged plasmids) and mass spectrometry. Finally, we will investigate whether ciliary proteins regulate trafficking of transcriptional regulators by confirming interactions with known transcription factors (Co-IP, GST-Pull downs) and examining expression of target genes comparing control and cilia knockout cell lines (RNAseq).
Publications relevant to the project
Gascue C, Tan PL, Cardenas-Rodriguez M, Badano JL. (2012). Direct role of Bardet-Biedl syndrome proteins in transcriptional regulation. J Cell Sci, 125: 362–375.
Hodges ME, Scheumann N, Wickstead B, Langdale JA and Gull K. (2010). Reconstructing the evolutionary history of the centriole from protein components. J Cell Sci, 123: 1407–1413.
van Dam TJP, Townsend MJ, Turk M, Huynen MA. (2013). Evolution of modular intraflagellar transport from a coatomerlike progenitor. Proc Natl Acad Sci USA, 110: 6943–6948.