PhD Studentship at MRC-NIMR, UK in Vertebrate Developmental Biology

DEVELOPMENTAL PATTERNING OF THE VERTEBRATE NERVOUS SYSTEM

NIMR project supervisor: James Briscoe (Developmental Biology)

The complex tissues and organs of every multicellular organism develop in a precise and reproducible manner from initially indistinguishable cells. A fundamental question is how such equipotent cells acquire the appropriate identity for their location. One example of this is the vertebrate central nervous system where the generation of an extraordinary array of neurons with distinct properties and functions is required for the assembly of neuronal circuits. In many developing tissues, including the CNS, naïve cells interpret graded signals, termed morphogens, as positional cues that organize the pattern of cellular differentiation. Our goal is to understand the molecular mechanisms controlling this process.

In ventral regions of the CNS, the secreted protein Sonic Hedgehog (Shh) acts as a morphogen to induce five progenitor domains in precise spatial order in the neural tube. Each progenitor domain is distinguished by the expression of different combinations of transcription factors and each domain generates a distinct neuronal subtype. The mechanism that produces this pattern remains poorly understood. To address this, we will use a combination of in vivo experimental manipulation and in silico analysis that will systematically decipher and model the neural tube network. The function of factors identified by these approaches will be examined and used to build, challenge and refine a model of neural tube development. The identification of the players and their functions within the network will offer insight into the mechanisms and principles controlling neural tube development. Moreover, since the operations of gene regulatory programmes underpin the development of all tissues we anticipate that our analysis will have broad implications for the development of many tissues. Collaborations with physicists and computational biologists have been established to support data analysis. This proposal offers interdisciplinary training in cutting edge techniques that will provide novel insight into transcriptional networks that control cell identity.

To apply: Please download and complete the Application Form and send it to studentships@nimr.mrc.ac.uk. The deadline for applications is on Sunday 23rd March 2014. On receipt of your application your two referees will be contacted. The deadline for submission of references is 12:00 noon (GMT) on Friday 28th March 2014. Your application may not be considered until your references are in place.

References

• Balaskas, N; Ribeiro, A; Panovska, J; Dessaud, E; Sasai, N; Page, Karen M; Briscoe, J and Ribes, V (2012)
  Gene regulatory logic for reading the Sonic Hedgehog signaling gradient in the vertebrate neural tube.
  Cell 148, 273-284 
  
• Jacob, J; Kong, J; Moore, S; Milton, C; Sasai, N; Gonzalez-Quevedo, R; Terriente, J; Imayoshi, I; Kageyama, R; Wilkinson, David G; Novitch, Bennett G and Briscoe, J (2013)
  Retinoid acid specifies neuronal identity through graded expression of Ascl1.
  Current Biology 23, 412-418 
  
• Cohen, M; Briscoe, J and Blassberg, R (2013)
  Morphogen interpretation: the transcriptional logic of neural tube patterning.
  Current Opinion in Genetics & Development 23, 423-428 
  

(No Ratings Yet)

Loading...