FP7Individual fellowship2014–2016

FORMALBIO · Protein Synthesis Control by Means of Formal Models

FP7 — People (Marie Curie Actions)

Duration
2014-10-01 → 2016-10-15
EU contribution
€309,235
Participants
1
Scheme
MC-IEF

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Results in brief

Protein Synthesis Control by Means of Formal Models

Proteins play essential roles in all living organisms, including humans. The excess or shortage of a particular protein can lead to health problems, e.g.. lack of insulin can lead to diabetes. Today, some proteins required by humans can be produced by micro-organisms as bacteria or yeast. The biological processes involved in the protein production are complex and difficult to control. The goal of this project is to study in detail the mechanism by which proteins are synthesized in order to optimize their production. In order to analyse and optimize a given biological system, a mathematical description of its mechanisms is required. Developing such a description is a challenging task mainly due to the paucity and heterogeneity of the available biological data. This project has overcome this problem by developing a novel set of mathematical tools, called Flexible Nets, that enables scientists to describe, analyse and control biological systems that are poorly characterized. Flexible Nets provide a graphical representation of the biological system under study, and can accommodate in a single system description uncertain data from different sources. Several methods have been designed along this project in order to analyse and control biological systems that are described in terms of Flexible Nets. These methods have been tested against well studied systems as the glucose consumption in yeast, and against poorly defined systems as the accumulation of copper in individuals suffering from Wilson’s disease. The research results attained so far have been presented in scientific conferences and submitted to international research journals. The outcome of this project is expected to help to better understand the biological processes going on in a cell. A profound knowledge of such processes could lead to the development of control approaches not only to optimize the protein synthesis but also to, for instance, reprogram the cell metabolism to enhance renewable and sustainable fuel production, or look for druggable vulnerabilities of cancer networks for improved anticancer therapeutics.

Data: CORDIS, © European Union

Project objective

Many biological systems at cellular level consist of a high number of elements interacting in complex patterns. These systems often exhibit emergent behaviours that cannot be detected by reductionist approaches. Systems biology is the interdisciplinary methodology aiming at understanding the dynamics of life by determining how the elements of a biological system interact to form functional networks. This research proposal intends to make to advance the state-of-the-art in systems biology by making systematic use of formal models, and more precisely of the Petri nets formalism.The research will focus on the network of interactions involved in the protein synthesis in Saccharomyces cerevisiae, a species of yeast. The overall goal of the proposal is to optimize the recombinant protein synthesis in this organism. This goal is to be achieved by means of three primary objectives: 1) to formally model the recombinant protein synthesis mechanism; 2) to analyse the obtained model by using formal methods; 3) to control the system behaviour to maximize the recombinant protein synthesis.The Petri net to be designed will model the different events taking place in the protein synthesis mechanism: transcription, translation, modification, transportation, degradation and secretion. The analysis of the Petri net will consider structural and dynamical properties, and special attention will be paid to the computation of throughput bounds and bottleneck identification. As bottlenecks constrain the throughput of the whole system, any control action aiming at maximizing the protein synthesis will be performed on them.Overall, this proposal intends to improve our understanding of the cellular mechanism regulating protein synthesis by providing mathematical modelling and analysis tools. This understanding will eventually enable us to control and optimize the synthesis of recombinant proteins, which are broadly used for vaccines, diagnostic tools and therapeutic purposes.

Original text from CORDIS.

Participants

  • THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGECoordinatorUnited Kingdom

Links

Data: CORDIS, © European Union