Sussex Neuroscience

Professor Claudio Alonso

ClaudioRNA regulation during Drosophila neural development

PROJECT SUMMARY

The Hox genes encode a family of transcription factors that guide the formation of animals by instructing cells to adopt different fates along the head-to-tail axis. The remarkable evolutionary conservation of the Hox genes all the way from fruit flies to human together with their roles in many human pathologies brings this important gene family to the focus of many areas in modern biomedical research [1, 8-14].

The Alonso Lab investigates the molecular mechanisms that regulate the expression of Hox genes in the Drosophila nervous system, with a focus on RNA regulation. Indeed, recent work in the lab [1-7] showed that regulation by microRNAs (miRNAs) and mRNA processing –a molecular process able to produce more than one mRNA from each gene– are important for the control of Hox gene expression and function during neural development in the fly.

In this project we will investigate the molecular basis and biological roles of Hox gene regulation via mRNA processing and miRNAs during the formation of the nervous system in the fruitfly Drosophila melanogaster. The fly is a powerful experimental model to study gene regulation and its effects on specific cells and tissues. The experimental approach will be based on the use of a range of state-of-the-art molecular, imaging and transcriptomic techniques in developing embryos.

The work is expected to contribute to the understanding of the roles of RNA regulation during the formation of complex tissues like the central nervous system.

The successful candidate will be a dynamic and committed student with strong interests in Molecular, Cellular and/or Developmental Neuroscience; candidates from other fields (especially physicists interested in biological problems) are also welcome to apply.

The Alonso Lab is a competitive and dynamic laboratory generously funded by a long-term Wellcome Trust Investigator Award made to Claudio Alonso in 2012. The team is driven by an international group of talented PhD students and post-docs with diverse backgrounds including Molecular Biology, Developmental Genetics, Neurobiology and Bioinformatics. The common denominator across all members is our strong commitment to understand how neural development is molecularly controlled.

REFERENCES

(N.B. to see all our papers go to the Alonso lab pages on the School of Life Sciences website) 

  1. Mallo, M. and Alonso C.R. (2013) The regulation of Hox gene expression during animal development, Development (in press)
  2. Alonso C.R. (2012) A complex 'mRNA degradation code' controls gene expression during animal development, Trends in Genetics, 28(2):78-88
  3. Patraquim, P., Warnefors, M. and Alonso, C.R. (2011) Evolution of Hox post-transcriptional regulation by alternative polyadenylation and microRNA modulation within twelve Drosophila genomes, Mol. Biol. Evol, 28(9): 2453-60
  4. de Navas, L.F., Reed, H.C., Akam, M, Barrio, R., Alonso, C.R., and Sánchez-Herrero, E. (2011) Integration of RNA processing and expression level control modulates the function of the Drosophila Hox gene Ultrabithorax during adult development, Development, 138 (1): 107-116
  5. Thomsen, S., Azzam, G., Kaschula, R., Williams, L.S. and Alonso, C.R. (2010) Developmental RNA processing of 3’UTRs in Hox mRNAs as a context-dependent mechanism modulating visibility to microRNAs, Development, 137 (17): 2951-2960.
  6. Thomsen, S., Anders, S., Janga S.C., Huber, W. and Alonso, C.R. (2010) Genome-wide analysis of RNA decay patterns during early Drosophila development, Genome Biology 11 (9):R93 [Selected for Genome Biology "Editors' Picks"]
  7. Reed, H.C., Hoare, T., Weaver T.A., White, R.A.H., Akam, M. and Alonso, C.R. (2010) Alternative splicing modulates Ubx protein function in Drosophila melanogaster, Genetics, 184 (3): 745-58. [Epub 2009 Dec 28][Selected for the “Highlights” section of Genetics]
  8. Alonso, C.R. (2008) The molecular biology underlying developmental evolution, Chapter 5, pp 80-99, in “EVOLVING PATHWAYS” Key Themes in Evolutionary Developmental Biology, Eds. Minelli, A. and Fusco, G., Cambridge University Press.
  9. Alonso, C.R. and Wilkins A.S. (2005) The molecular elements that underlie developmental evolution, Nature Reviews Genetics, 6(9): 709-715
  10. Alonso, C.R. (2005) Nonsense-mediated RNA decay: a molecular system micromanaging individual gene activities and suppressing genomic noise, BioEssays, 27 (5):463-6
  11. De la Mata, M., Alonso, C.R., Kadener, S., Fededa J.P., Blaustein M., Pelisch, F., Cramer, P., Bentley, D. and Kornblihtt, A.R. (2003) A slow RNA polymerase II affects alternative splicing in vivo. Molecular Cell, 12 (2): 525–532. [EXCEPTIONAL Faculty of 1000 Biology, see Bickmore W: 2003. F1000.com/1015585***][see News&Views article in Nature Struct Mol Biol (2003)10:876-878)]
  12. Alonso, C.R. and Akam, M. (2003) A Hox gene mutation that triggers Nonsense-mediated RNA decay and affects alternative splicing during Drosophila development, Nucleic Acids Res., 31 (14): 3873-80.
  13. Alonso, C.R. (2002) Hox Proteins: Sculpting Body Parts by Activating Localised Cell Death, Current Biology, 12 (22): R776-R778.
  14. Alonso, C.R., Maxton-Küchenmeister, J. & Akam, M.E. (2001) Evolution of Ftz protein function in insects, Current Biology, 11(18):1473-1478