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De novo protein discovery as a tool for understanding the folding conundrum

Objective

Order is a prerequisite for activity, which is the essence of the sequence-structure-function paradigm of bio-macromolecules. Proteins are a case in point, displaying intricate architectures and impressive functions. Understanding how the primary sequence of these complex macromolecules relates to their 3D structure and vice versa is of fundamental interest and the basis for broad technological exploitation of proteins.
The proposed research aims to investigate the folding space of proteins, gaining new insights that will help in solving the folding conundrum. Specifically, the frequency and sequence patterns of ordered polypeptides and their physical and structural properties will be experimentally analysed. Based on these data sets, exploratory data analysis can be performed, providing unprecedented insights into protein folding. Generation of quantifiable high quality data is thus of utmost importance for this project. One of the main objectives of this proposal is therefore the development of an ultrahigh-throughput experimental platform for discovery of de novo proteins with unparalleled precision, using state-of-the-art molecular biology methods. Based on cutting-edge mRNA display technology, I will isolate folded polypeptides from naïve libraries with up to 1E13 members in the size range of 50-100 amino acids. Modern bioinformatic analysis, modelling and biophysical characterisation will be performed to analyse the folding space of proteins and derive new empirical folding rules.
Given the increasing importance of protein engineering in fundamental research and industry, the results of this study will be of interest to a wide range of scientists. The fellowship will provide training in state-of-the-art techniques such as statistical data analysis and structural biology. The results of this research project will form the basis for future efforts to exploit the biotechnological potential of newly discovered proteins.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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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.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2017

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Coordinator

UNIVERSITY OF BRISTOL
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 183 454,80
Address
BEACON HOUSE QUEENS ROAD
BS8 1QU BRISTOL
United Kingdom

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Region
South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Bristol, City of
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 183 454,80
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