We would like to invite you to attend this seminar hosted by A/Prof. Sudipto Roy:
Date: 26 February 2015, Thursday
Time: 3:00PM – 4:00PM
Venue: Level 3, IMCB Seminar Room 3-46, Proteos, Biopolis
Speaker: Dr. Dominic Norris, Programme Leader, Cilia, Development and Disease, MRC Harwell, United Kingdom
Title: Cilia, flow and polycystins: telling left from right
While externally mirror symmetrical, vertebrates show clear left-right (L-R) asymmetry in the positioning and patterning of their internal organs and vasculature. This is evolutionarily conserved, reflecting both its ancient origin and physiological significance. In early embryos, while L-R is mathematically obvious, cells must still gain a left or right identity. The initial breaking of symmetry occurs when motile cilia in the embryonic node (a transient pit shaped structure) rotate, driving a leftward fluid flow. This biophysical force, known as nodal flow, is itself ‘perceived’ in a cilia dependent manner. The mechanisms involved remain controversial. In this talk I will discuss our work on the role of cilia and in particular two polycystin proteins, PKD1L1 and PKD2; all are required for normal L-R patterning. I will provide evidence that PKD1L1 is a strong candidate to be the elusive sensor of flow, showing that it acts downstream of flow but upstream of early gene expression asymmetries. Furthermore, our genetic experiments have revealed a novel pathway linking the generation and sensation of flow to the establishment of asymmetric gene expression. Finally, I discuss a small extracellular domain of PKD1L1 that is essential for function and might be central to the mechanism of flow sensation.
During his PhD in London, Dr Norris was trained in mouse genetics; he studied X-chromosome inactivation, demonstrating that CpG methylation controlled imprinting of the Xist locus. As a post-doc, in Harvard, he trained in developmental biology, transgenesis and stem cell biology. While studying the control of the Nodal locus, Dr Norris became intrigued by the mechanisms underlying left-right (L-R) determination. On his return to the UK he combined his interests in developmental biology and mouse genetics, establishing a genetic screen to identify novel loci affecting L-R patterning. Out of the results of this screen came a new interest in cilia and cilia biology. Subsequent studies have identified Dnah11 mutants as models of Primary Ciliary Dyskinesia; Atmin as encoding an important cilia transcription actor; and the products of Pkd1l1 and Pkd2 as key of molecules that respond to flow and establish the L-R axis.
ALL ARE WELCOME (No registration required)
For upcoming seminars in IMCB, please visit our website at http://www.imcb.a-star.edu.sg/php/seminars.php