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INRA 
EVOLUTIONARY HISTORY OF AUTOPHAGY RELATED GENES IN FISH
INRA-UPPA, Saint Pée-sur-Nivelle
UMR1419 NuMeA
Evolution Molecular Biology Bioinformatics 
Full Description:

BACKGROUND AND OBJECTIVES

Autophagy is an evolutionarily conserved process in eukaryotes by which cytoplasmic cargo sequestered inside double-membrane vesicles are delivered to the lysosome for degradation. This 'self-eating' process not only rids the cell of intracellular misfolded proteins or damaged organelles, but is also a key adaptive response to provide energy when nutrients are scarce. Dysregulation of autophagy has been implicated in numerous human disease such as neurodegenerative diseases, infectious diseases, and cancers.

Although research on autophagy has expanded dramatically in the past 10-15 years, it has been mainly focused on mammalian models, particularly in the context of human diseases. Due to a general lack of work with other vertebrate taxa, it still remains unknown whether the mammalian autophagy genes (atg) repertoire as well as the related expression patterns and functions is even representative of the remaining ninety percent of vertebrate species, where autophagy is just as crucial for survival. In this regard, recent findings demonstrated that while 90% of the “autophagy core” genes are conserved across all eukaryotic species, those coding for proteins involved in the recognition of substrates to be degraded by autophagy display a rather low conservation in ancient taxa, suggesting a specialization of this function during evolution. Furthermore, it is possible that the whole genome duplication occurred 300-350 million years ago in the common ancestor of teleosts (ray-finned fishes gathering 99.8% of current fish species and almost half of vertebrate species) has strongly modulated the genetic structure and therefore the function of autophagy in this group of fish compared to mammals.

In this context, the project we propose aims to characterize the landscape of atg genes (20-30 gene families) in the genome of teleost and non-teleost fish species covering a large period of the evolutionary history of vertebrate and describe their evolutionary history. The growing number of fish species whose genome was completely sequenced and recent advances in transcriptome analysis allows today to include in the study a large number of species and thus to trace the evolutionary history of autophagy-related genes.

 

REFERENCES

· Seiliez et al. (2016). Looking at the metabolic consequences of the colchicine-based in vivo autophagic flux assay. Autophagy, 12(2):343-56.

· Klionsky, D.J. et al. (2467 co-authors including Seiliez) (2016). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy, 12(1):1-222.

· Seiliez et al. (2012). Amino acids downregulate the expression of several autophagy-related genes in rainbow trout myoblasts. Autophagy, 8 (3), 1-12.

· Berthelot et al. (2014) The rainbow trout genome provides novel insights into evolution after whole-genome duplication in vertebrates. Nat Commun 5:3657.

 

REQUIRED SKILLS AND KNOWLEDGE            

Solid bases in bioinformatics and/or molecular biology are required. Knowledge in evolutionary biology will be highly appreciated. English (reading and writing) is mandatory.

 

REQUIRED DOCUMENTS

CV ; Letter of Motivation ; reports ; certificates ; contact names and addresses of references (at least two) familiar with the work of the candidate

 

APPLICATION DEADLINE: 15 April

Contact : Iban  SEILIEZ (seiliez@st-pee.inra.fr)

 



Posted on: 24 March 2016Deadline to apply: 15 April 2016Start Date: 01 October 2016 Duration: 36 months
The Fund category is Public Funding - University and the salary is 20-25k€ annual gross
Doctoral School is Exact sciences and their applications in the Aquitaine Region.

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