EVO-DEVOMICS · Decoding developmental gene regulatory programs by evolutionary transcriptomics
FP7 — People (Marie Curie Actions)
- Duration
- 2009-09-01 → 2013-08-31
- EU contribution
- €100,000
- Participants
- 1
- Scheme
- MC-IRG
Lines connect the coordinator with its partners.
Results in brief
Decoding developmental gene regulatory programs by evolutionary transcriptomics
Marie Curie International Reintegration Grants (IRG) Call: FP7-PEOPLE-IRG-2008 “EVO-DEVOMICS” - DECODING DEVELOPMENTAL GENE REGULATORY PROGRAMS BY EVOLUTIONARY TRANSCRIPTOMICS The goals of the proposed research were to: 1) to construct a molecular atlas for the developmental gene regulatory programs of seven nematode species and to test a model for developmental reprogramming, and 2) to directly test developmental reprogramming predictions in endoderm specification. A description of the work performed since the beginning of the project, 1. An atlas for developmental gene regulatory programs across nematode embryology was constructed. Using this dataset, it was discovered that developmental milestones punctuate gene expression. The results were published in the journal Developmental Cell: a. http://www.cell.com/developmental-cell/abstract/S1534-5807(12)00142-6 b. It was highlighted with a Preview article: http://www.cell.com/developmental-cell/abstract/S1534-5807(12)00198-0 2. A method for single cell RNA-Seq was developed which was both highly multiplexed and dependent upon linear amplification. This method was published in Cell Reports: a. http://www.cell.com/cell-reports/abstract/S2211-1247(12)00228-8 b. It was highlighted in a recent review: http://www.nature.com/nrg/journal/v14/n9/full/nrg3542.html 3. We discovered a genomic bias for genotype-environment interactions in the C. elegans genome by examining gene expression of the C. elegans early embryo across five strains in five different conditions. We reported our findings in the journal Molecular Systems Biology. a. http://www.nature.com/msb/journal/v8/n1/full/msb201219.html b. We were also invited to submit a Review on these results in the journal Trends in Genetics: http://www.sciencedirect.com/science/article/pii/S0168952513000851 Expected final results and their potential impact. The final results have already been published and their impact already in sight. First, the atlas is being used by researchers of C. elegans. For every gene, users of the Wormbase site can see the gene expression profile from our atlas. For example, here is the profile for the gene tbx-43: http://www.wormbase.org/species/all/expr_pattern/Expr1012093#021--10. The Levin et al publication arising from this work (link above) has already cited 16 times since publication in 2012. A series of experiments have been planned following this work which has recently received funding from the ERC to the researcher (Itai Yanai). The CEL-Seq protocol developed as part of this project is a very successful method now used by many labs worldwide. Using this method, it is possible for any lab to examine individual cells at the whole transcriptomic level. Third, we discovered one important genomic biases for genotype-environment interactions. Though the work was done in the worm C. elegans, the insight derived there for the importance of trans effects is applicable to humans for detecting the advese effects of medicine. We are now collaborating with members of our medical school to follow up on this insight. The works can be reviewed here: http://yanailab.technion.ac.il/
Data: CORDIS, © European Union
Project objective
An animal’s ability to build itself from a single cell is arguably the most amazing phenomenon of the living world. This process follows from an intricate regulation of the genome, however, deciphering this program remains largely an unsolved problem. The premise of the proposed research program is that an organisms’ regulatory program is a product of evolution and needs to be analyzed as such. My approach is thus to study gene regulation on a phylogeny of organisms, by constructing an atlas of gene expression profiles across developmental stages for a set of 12 nematodes. Such a dataset would constitute the first analysis of genomic regulatory elements with sufficient instances of sequence programs and the corresponding expression regulations to enable comprehensive study. I propose to analyze this dataset with an algorithm that matches specific patterns of presences and absences of expression elements within a homologous group to the corresponding regulatory sequences; putative cis-regulatory sites will then be experimentally tested for the predicted pattern specific expression. In particular, I propose to search for the evolutionary principles such as heterochrony and heterotypy that underlie the evolution of gene regulatory networks, with a special focus on the mode of selection of each element of a gene’s expression profile. As a model system, I will focus on the genetic specification of the C. elegans endoderm, using advanced embryological techniques coupled with inferences from comparisons of endoderm specification across the phylum, to attempt to reprogram its development. In parallel, I shall seek to test for the universality of the observed evolutionary principles, through an analysis of available datasets across the animal kingdom. Progress along this research program aims to contribute to the broad goal of deciphering genomic regulatory networks, as well as to an understanding for how developmental processes are reprogrammed throughout evolution.
Original text from CORDIS.
Participants
- TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY · HaifaCoordinatorIsrael
Links
Data: CORDIS, © European Union