Obiettivo
The advent of recombinant DNA technique, provides us with the tools required to exploit bacteria for production of novel products of high biotechnological value. The potential of bacteria lies also in their ability to grow to high cell densities and to produce the required protein product as a large part of their biomass. Although there is a high degree of industrial interest, the number of recombinant protein products that are on the market or under development is low in comparison with the commercial expectations and the current level of investment.
When new industrial production strategies are being developed, severe time constraints imposed by commercialization, necessitates the use of empirical approaches. These are currently based on a small range of overexpression systems. Such approaches are only permissible if the final output is sufficiently high and valuable. After regulatory approval, it is generally too late and too expensive to modify the process. However, as the value of recombinant products declines with increasing competition, there is a demand for improved process optimization. A lack of knowledge of steering parameters does not, however, permit the optimization procedure to be performed on rational scientific basis. Additionally, the limited time available for process development does not, in most cases, allow for the control of unexpected variations in product quality and quantity caused for example by differences in batches and scale-up effects.
A basic concept of this project is that the strategy for process development is often constrained by a limited understanding of:
(i)recombinant protein overexpression in relation to the availability of intracellular building blocks and energy
(ii) the contemporaneous need for to satisfy the energy requirements for cell maintenance
(iii) the status of the intracellular building blocks and energy in relation to the possibilities of supply of exogenous sources.
From the above it is apparent that effective process development will involve the use of expertise ranging from molecular biology, microbial physiology to biochemical engineering.
The long term goal of this project is to derive a strategy that can be used for bioprocess development in order to: (i) arrive at regulatory approval with higher confidence; (ii) avoid wasteful and inefficient process performance and; (iii) provide knowledge of bottlenecks common to the general process. This will allow a true optimization procedure to be developed with a better understanding of the reasons for batch and scale-up variations.
The project strategy is based on prior knowledge that bottlenecks influencing process performance are to be found both within the cell in relation to the design of the bioprocess and from limitations in bioreactor capacity for oxygen and heat transfer.
In order to achieve the long term goal of the project we will focus on providing answers to the following issues;
1 the design of an optimal promoter and ribosomal binding site favourable for the induction of protein production under process conditions 2 the control of substrate uptake and intracellular metabolite balance to avoid energy and/or precursor limitation and to eliminate the waste of energy during production
3 the process optimization, based on the-parameters of the feed protocol and taking into account; (i) intracellular bottlenecks at selected growth rates and; (ii) limitations in oxygen and heat transfer at various cell growth and/or production rates
For successful evaluation and strategy development for production of recombinant proteins, it is necessary to derive the reasons why bacterial populations under the conditions described above often form in sub-populations some of which some are nonproductive and some not viable. We will therefore develop non-invasive techniques to measure the production capacity and viability per individual cell.
We believe this strategy to be generic since the regulatory elements are common to all living cells irrespective of environmental shifts. The strategy is therefore valid irrespective of whether the cells are grown in a reactor or in the natural environment. The present model system was chosen because it exhibits the highest level of prior knowledge and is combined with a system designed to diminish the effects of bottlenecks that are outside the scope of this project.
Campo scientifico (EuroSciVoc)
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: Il Vocabolario Scientifico Europeo.
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: Il Vocabolario Scientifico Europeo.
- ingegneria e tecnologia biotecnologia ambientale biorisanamento bioreattori
- ingegneria e tecnologia ingegneria chimica ingegneria biochimica
- scienze naturali scienze biologiche microbiologia batteriologia
- scienze naturali scienze biologiche biochimica biomolecole proteine
- scienze naturali scienze biologiche biologia molecolare
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Programma(i)
Programmi di finanziamento pluriennali che definiscono le priorità dell’UE in materia di ricerca e innovazione.
Programmi di finanziamento pluriennali che definiscono le priorità dell’UE in materia di ricerca e innovazione.
Argomento(i)
Gli inviti a presentare proposte sono suddivisi per argomenti. Un argomento definisce un’area o un tema specifico per il quale i candidati possono presentare proposte. La descrizione di un argomento comprende il suo ambito specifico e l’impatto previsto del progetto finanziato.
Gli inviti a presentare proposte sono suddivisi per argomenti. Un argomento definisce un’area o un tema specifico per il quale i candidati possono presentare proposte. La descrizione di un argomento comprende il suo ambito specifico e l’impatto previsto del progetto finanziato.
Invito a presentare proposte
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Procedura per invitare i candidati a presentare proposte di progetti, con l’obiettivo di ricevere finanziamenti dall’UE.
Meccanismo di finanziamento
Meccanismo di finanziamento (o «Tipo di azione») all’interno di un programma con caratteristiche comuni. Specifica: l’ambito di ciò che viene finanziato; il tasso di rimborso; i criteri di valutazione specifici per qualificarsi per il finanziamento; l’uso di forme semplificate di costi come gli importi forfettari.
Meccanismo di finanziamento (o «Tipo di azione») all’interno di un programma con caratteristiche comuni. Specifica: l’ambito di ciò che viene finanziato; il tasso di rimborso; i criteri di valutazione specifici per qualificarsi per il finanziamento; l’uso di forme semplificate di costi come gli importi forfettari.
Coordinatore
100 44 STOCKHOLM
Svezia
I costi totali sostenuti dall’organizzazione per partecipare al progetto, compresi i costi diretti e indiretti. Questo importo è un sottoinsieme del bilancio complessivo del progetto.