All Seminars are held in the Gavin De Beer Lecture Theatre, Anatomy Building, Thursday 1-2pm (unless otherwise stated)
Thursday 9 July: midday-2.40pm
Host: Yoshiyuki Yamamoto
Room 249, 2nd Floor, Medical Sciences Building, Gower Street
Steele-Stallard: “Human iPS cell-based platforms for disease modelling and
therapy screening for laminopathies”
Dr Leslie Dale
Leslie Dale is a Reader in Developmental Biology, using the amphibian Xenopus laevis as a model organism to analyse gene function during embryonic development.
We are interested in how the embryo of the frog Xenopus laevis develops from a fertilized egg into a swimming tadpole. Our current research has focussed on the roles of two gene families: the Tolloid family of metalloproteases and the P2Y family of G-protein coupled receptors (GPCRs).
We have identified 3 members of the Tolloid family in early Xenopus embryos and shown that they are required for dorsal-ventral patterning during gastrulation. Increasing activity ventralizes embryos while decreasing activity dorsalizes them. We have shown that their function is to modulate the activity of BMP4, a key ventralizing signal, by cleaving Chordin, a BMP inhibitor. Cleavage by Tolloids reduces the affinity of Chordin for BMPs, thereby increasing BMP activity.
A second project explores the roles of members of the P2Y family in Xenopus development. We have cloned several members of this family that are expressed in Xenopus embryos and shown that two of them (P2Y8 AND P2Y11) are receptors for extracellular nucleotides (e.g. ATP). Inhibition of the latter generates defects in several tissues, including the nervous system. We have also shown that P2Y5, an orphan receptor, is required in brain development.
Recently, we have begun a collaborative project with the laboratory of Dr S Patel, characterising Xenopus ADP-Ribosyl cyclases. These enzymes synthesize calcium releasing second messengers such as cADPR and NAADP. We have evidence that they are required for differentiation of skeketal muscle in Xenopus embryos.
University of Sussex
1977-1979 Research Assistant, University of Essex
1979-1982 Research Assistant, University of Edinburgh
1983 PhD, University of Edinburgh
1983-1985 Research Fellow, ICRF, Mill Hill Labs
1985-1987 Research Fellow, ICRF, Oxford
1987 Research Fellow, University of Warwick
1987-1993 Research Fellow, University of Birmingham
1993 Lecturer, UCL
2000 Reader, UCL
- Dale L, Evans W, Goodman SA (2002). Xolloid-related: A novel BMP1/Tolloid-related metalloprotease is expressed during early Xenopus development. Mech. Dev. 119: 177-190.
- Geach TJ, Dale L (2005). Members of the Lysyl Oxidase family are expressed during development of the frog Xenopus laevis. Differentiation 73: 414-424.
- Devader C, Webb R, Thomas G, Dale L (2006). Xenopus apyrase (xapy), an ectonucleotidase that is expressed during early development. Gene 367: 135-141.
- Churamani D, Boulware MJ, Geach TJ, Andrew C. R. Martin ACR, Moy GW, Su YH, Vacquier VD, Marchant JS, Dale L, Patel S (2007). Molecular characterization of a novel intracellular ADP-Ribosyl Cyclase. PLoS ONE 2: e797.
- Devader C, Drew CM, Geach TJ, Tabler J, Townsend-Nicholson A, Dale L (2007). A Novel nucleotide receptor in Xenopus activates the cAMP second messenger pathway. FEBS Lett 581: 5332-5336.
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