Objective
Circadian 24 hrs patterns of behaviour and physiology are ubiquitous in animals and plants, from bacteria to humans. Recent analyses of the molecules involved in biological rhythmicity in the fly Drosophila melanogaster and in the bread mould Neurospora crassa reveal that the key timing molecules seem to act in similar ways, suggesting that solving the problem of biological timing for one organism will serve to unravel a common molecular mechanism for all organisms. In Drosophila melanogaster, where the greatest advances have been made, two proteins PERIOD (PER) and TIMELESS (TIM), interact to generate circadian rhythmicity. They are both negative regulators of the* own transcription and they dimerise in the cytoplasm before entering the nucleus. The binding domain of PER involves a 280 amino acid region termed PAS, whereas the corresponding domain for TIM includes about 400 amino acids. Mutations which disrupt this association produce dramatic changes in periodicity. However, other than a general appreciation of the relevant dimerization domains of the two proteins, almost nothing is known about how timing information is transmitted from the cytoplasm to the nucleus.
The per gene evolves relatively quickly, and evidence from two of our laboratories suggests that the PER-TIM interaction may co-evolve, so that PER from one Dipteran species does not dimerise well to TIM from another. A comparative structure/ function approach will be used where we will initially examine the relevant sequences from the per and tim genes in a variety of Dipteran species and study their homo and heterospecific binding abilities using a yeast assay which tests for protein-protein interactions. We will simultaneously determine the molecular 'shapes' of the PER and TIM interacting surfaces in Drosophila using state-of-the-art conformational methods. The results of the conformational and yeast analyses will identify regions in the PER and TIM domains that will be critical for binding. These will be mutagenized, and tested for their binding function using both the yeast assay, and a behavioural assay of circadian behaviour. Solving the conformational structure of the two interacting domains of PER and TIM, and knowing which are the critical regions for their association may have wide applications in a number of different fields, including human health, agriculture and in the pharmaceutical industry.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences microbiology bacteriology
- natural sciences biological sciences genetics mutation
- natural sciences mathematics pure mathematics mathematical analysis functional analysis
- natural sciences chemical sciences organic chemistry amines
You need to log in or register to use this function
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Data not available
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
LE1 7RH Leicester
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.