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CDB Seminars
All welcome

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All Seminars are held in the Gavin De Beer Lecture Theatre, Anatomy Building, Thursday 1-2pm

2 Oct: Helena (Wilson lab) /Maria Maiaru (Geranton lab)

16 Oct: Tom Wyatt (Charras lab) (Oates lab)

30 Oct: Harold Burgess - Title TBC (Host: Prof Steve Wilson)

31 Oct: SPECIAL SEMINAR - Sophie Jarriault (IGBMC) – Title TBC (Host: Dr Richard Poole)

6 Nov: Aude Marzo (Salinas lab)/ Maite Ogueta (Stanewsky lab)

13 Nov: (Paluch lab)/ Robert Bentham (Szabadkai lab)

27 Nov: Irene (Stern lab)/Cristina Benito(Jessen lab)

11 Dec: Marcus Ghosh (Rihel lab)/ (Chubbs lab)

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Wellcome PhD Students: Final Year Talks

Thursday 25 September

12.30-2.35pm

Room 249, 2nd Floor, Medical Sciences Building, Gower Street

12.30pm:  Scott Curran: “Annealing: the changing role of junctional actomyosin in epithelial cell packing during tissue development”

12.55pm:  Kristina Tubby: “The development of the avian auditory hindbrain”

1.20pm:  Miguel Tillo: “Signals controlling neuronal migration in the embryonic hindbrain”

1.45pm:  Alex Sinclair-Wilson: “Olig2 and regulation of neural stem cell fate”

2.10pm:  Elena Scarpa: “Cadherin-Dependent Rac1 Polarity acquired during Epithelial to Mesenchymal Transition triggers Contact inhibition of Locomotion”

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Professor Chris Danpure

Prof Chris Danpure


Chris Danpure, PhD FMedSci
Professor of Molecular Cell Biology


Contact:

c.danpure@ucl.ac.uk


tel: (+44)-(0)20-7679-7936
fax: (+44)-(0)20-7679-7096

Academic Career

2008-present
Research Department of Cell and Developmental Biology, UCL

1994-2008
Department of Biology, UCL

1994-2001
MRC Laboratory for Molecular Cell Biology

1973-1994
MRC Clinical Research Centre, Harrow

1971-1973
Beecham Research Laboratories, Harlow

1968-1971
PhD (Biochemistry) Institute of Cancer Research, University of London

1965-1968
BSc (Physiology & Biochemistry) University of Reading

Research

The intermediary metabolic enzyme alanine:glyoxylate aminotransferase (AGT) is unusual insofar as it can be targeted to different parts of the cell (i.e. peroxisomes and/or mitochondria) under different circumstances. Under the influence of dietary selection pressure, its subcellular distribution has changed on at least twenty occasions during the evolution of mammals. In extant species, AGT tends to be peroxisomal in herbivores, mitochondrial in carnivores, and both peroxisomal and mitochondrial in omnivores. AGT deficiency in humans leads to the autosomal recessive disorder primary hyperoxaluria type 1 (PH1), which is characterised by excessive synthesis and excretion of oxalate and the deposition of insoluble calcium oxalate in the kidney and urinary tract. In the largest single subset of patients, AGT is mistargeted from the peroxisomes to the mitochondria due to the synergistic interaction between a common polymorphism and a disease-specific mutation. Although still catalytically active, AGT is metabolically inefficient when mislocalized to human mitochondria.

Over the past fifteen years, my laboratory has been interested in elucidating the molecular and cellular bases of AGT targeting in both mammalian evolution and human hereditary disease. We have been especially interested in the mutational events that lead to changes in AGT targeting during mammalian evolution, as well as the molecular and cellular nature of the atypical behaviour of the peroxisomal targeting sequence in the human. In addition, we have been interested in elucidating the complex genotype-phenotype relationships in PH1 and how this information might be used in the development of new treatments. We have recently solved the crystal structure of human AGT and are currently looking at the development of targeting-based bioassays in order to test the effects of small molecules (chemical chaperones) that might stabilise AGT and counteract the effects of disease-causing mutations. Such drugs might have use not only for PH1, but also for the much more common idiopathic calcium oxalate kidney stone diseases.

References

  • Lumb, M.J., Birdsey, G.M. & Danpure, C.J. Correction of an enzyme trafficking defect in hereditary kidney stone disease in vitro. Biochem. J. 374, 79-87 (2003)
  • Zhang, X, Roe, S.M., Hou, Y., Bartlam, M., Rao, Z., Pearl, L.H. & Danpure, C.J. Crystal structure of alanine:glyoxylate aminotransferase and the relationship between genotype and enzymatic phenotype in primary hyperoxaluria type 1. J. Mol. Biol. 331, 643-652 (2003)
  • Danpure, C.J. & Rumsby, G. Molecular aetiology of primary hyperoxaluria and its implications for clinical management. Expert Rev. Mol. Med. 6, DOI: 10.1017/S1462399404007203 (2004)
  • Birdsey, G.M., Lewin, J., Cunningham, A.A., Bruford, M.W. & Danpure, C.J. Differential enzyme targeting as an evolutionary adaptation to herbivory in Carnivora. Mol. Biol. Evol. 21, 632-646 (2004)

Page last modified on 24 may 10 15:33 by Glenda Young