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iGEM 2018 Winners

28-10-2018 Synthetic Biology Competition winners!

The Valencia UPV 2018 IGEM tem won the Grand Prize at the iGEM competition of Synthetic Biology organized by MIT with its project Printeria!

New publication

03-07-2018 "Flux-dependent graphs for metabolic networks", Nature pj Systems Biology and Applications, 2018,  just accepted

Cells adapt their metabolic fluxes in response to changes in the environment. We present a framework for the systematic construction of flux-based graphs derived from organism-wide metabolic networks. Our graphs encode the directionality of metabolic flows via edges that represent the flow of metabolites from source to target reactions. The methodology can be applied in the absence of a specific biological context by modelling fluxes probabilistically, or can be tailored to different environmental conditions by incorporating flux distributions computed through constraint-based approaches such as Flux Balance Analysis. We illustrate our approach on the central carbon metabolism ofEscherichia coli and on a metabolic model of human hepatocytes. The flux-dependent graphs under various environmental conditions and genetic perturbations exhibit systemic changes in their topo- logical and community structure, which capture the re-routing of metabolic flows and the varying importance of specific reactions and pathways. By integrating constraint-based models and tools from network science, our framework allows the study of context-specific metabolic responses at a system level beyond standard pathway descriptions.

 

 

 

 

New PhD grant soon available

04/05/2018. PhD grant linked to project SynBioControl will be soon available. Computational metabolic network analysis for synthetic biology

 

Topic: Computational metabolic network analysis for synthetic biology

 

This position will be funded by the project  SynBioControl: Design, characterization and optimal tuning of synthetic biocircuits for bioproduction with control of the metabolic load  (MINECO/AEI/FEDER,UE  Grant DPI2017-82896-C2-1-R)

 

PROJECT SUMMARY:

 

The project SynBioControl has been granted by the MINECO/AEI/FEDER,UE  (Grant DPI2017-82896-C2-1-R). New The biotech industry of the immediate future will integrate complex synthetic genetic circuits into microorganisms used as cell factories to produce proteins and metabolites of industrial importance. To this end, it has to deal with several critical problems that currently limit the applicability of synthetic biology: the rational design of synthetic genetic circuits of increasing complexity, their experimental characterization and robust tuning, and their industrial scaling. One of the main factors hindering the solution of these problems is the modification of the expected behavior of the circuits designed as a consequence of metabolic and genetic load of the cell caused by usage of shared time-varying cellular resources. Managing these phenomena requires the redesign of the circuits and the addition of additional feedback control mechanisms in order to maintain the specified design behavior. In this line SynBioControl adopts synthetic biology as a discipline of engineering, and emphasizes the application of engineering principles and methodologies via strategies of feedback control, computational optimization and multivariate analysis.The project focuses on a practical challenge and two related general objectives:

- General Practical Challenge: Design and implementation of feedback control mechanisms of protein and metabolite expression with consideration of the effects of metabolic and genetic load.

- Methodological Objective 1: Development of methods of structural design, analysis and robust parametric tuning of synthetic control genetic circuits through multiobjective optimization.

- Methodological Objective 2: Development of data analytics methods and grey models with application to scaling-up from the laboratory to the pre-industrial bioreactor.

To achieve these goals we will make use of methods from the areas of applied mathematics, optimization, systems engineering and control, and multivariate statistics.

 

RESEARCH POSITION TASKS

 

This position deals with research in methods to link cell environmental conditions, metabolism, and  synthetic gene circuits. 

 

The candidate is expected to interact in a multidisciplinary team, comprising the SB2C Lab (Synthetic Biology and BioSystems Control Lab) and GIEM group (research group in multivariate statistical engineering) at the Technical University of Valencia, and the (Bio)process Engineering Group at IIM-CSIC. The candidate will be anchored at the SB2C Lab (Valencia, Spain) with Prof. Jesús Picó and Prof. Alberto Ferrer as supervisors. 

 

The ideal candidate should have a degree in engineering, applied maths, biophysics, physics or equivalent discipline, and have some proficiency in programming languages (e.g. Matlab, Maple).  Notice some background in biology, or the willingness to learn cell biology, and even basic biology laboratory skills, will be a requisite. 

 

CHARACTERISTICS OF THE POSITION

 

  • Gross salary around 1200€/month, 12+2 months/year.

  • There is also the option to obtain funding for conferences and on leave stays.

  • Duration of the contract: 4 years.

 

APPLICATION PROCESS

 

Please send a letter in English, including a personal motivation, your academic grades (including ranked position in the student cohort) and curriculum vitae, to Jesús Picó (jpico@ai2.upv.es) and Alberto Ferrer (aferrer@upv.es).

New granted project

Design, characterization and optimal tuning of synthetic biocircuits for bioproduction with control of the metabolic load (SynBioControl)

The project SynBioControl has been granted by the MINECO/AEI/FEDER,UE  (Grant DPI2017-82896-C2-1-R). New The biotech industry of the immediate future will integrate complex synthetic genetic circuits into microorganisms used as cell factories to produce proteins and metabolites of industrial importance. To this end, it has to deal with several critical problems that currently limit the applicability of synthetic biology: the rational design of synthetic genetic circuits of increasing complexity, their experimental characterization and robust tuning, and their industrial scaling. One of the main factors hindering the solution of these problems is the modification of the expected behavior of the circuits designed as a consequence of metabolic and genetic load of the cell caused by usage of shared time-varying cellular resources. Managing these phenomena requires the redesign of the circuits and the addition of additional feedback control mechanisms in order to maintain the specified design behavior. In this line SynBioControl adopts synthetic biology as a discipline of engineering, and emphasizes the application of engineering principles and methodologies via strategies of feedback control, computational optimization and multivariate analysis.

The project focuses on a practical challenge and two related general objectives:

- General Practical Challenge: Design and implementation of feedback control mechanisms of protein and metabolite expression with consideration of the effects of metabolic and genetic load.

- Methodological Objective 1: Development of methods of structural design, analysis and robust parametric tuning of synthetic control genetic circuits through multiobjective optimization.

- Methodological Objective 2: Development of data analytics methods and grey models with application to scaling-up from the laboratory to the pre-industrial bioreactor.

Two objectives will be considered transversal to the previous ones:

- Transversal Objective 1: Contribution to the conversion of Synthetic Biology into an engineering, making the modeling and design process more systematic (standardized), modular, predictable, and robust, with an emphasis on the development of methodologies that can be applied in an effective way in the practical environment of a standard industrial biotechnology laboratory.

- Transversal Objective 2: Implementation of open source software tools and devices or biological parts (biobricks) of public access, facilitating the dissemination of Synthetic Biology as an area of engineering.

In SynBioControl we will make use of essential enabling technologies (feedback control, computational optimization, and multivariate analysis) coupled with metabolic engineering and DNA synthesis and assembly, will provide the right solutions.

To achieve its objectives, SynBioControl integrates an academic group of systems engineering, control and statistics specialized in modeling and control of bioprocesses, systems and synthetic biology, multivariate statistics, monitoring, scaling of processes and analysis of omics data (SB2CLab/GIEM-UPV) and a chemical engineering group specialized in bioprocess engineering, including modelling and optimization in systems and synthetic biology (IIM-CSIC). In addition, the project includes Biopolis S.L. (http://www.biopolis.es/es/inicio/), a Valencian biotechnology company leader in Spain, belonging to the ADM group, and provider of R & D and production services for the agro-food, pharmaceutical, chemical and energy industries.

 

New publication

04-05-2018 "Output feedback linearization of turbidostats after time scaling", IEEE Trans. on Control Systems Technology, 2018,  just accepted

Turbidostats are a class of bioreactors gaining in- terest due to the recent availability of micro- and small-scale devices for characterization and scaling-up of biotechnological systems relevant in the biotech and pharma industries. The goal is to keep cell density constant in continuous operation. Thus the control law, i.e. the substrate feeding strategy, must guarantee global or semiglobal convergence to an equilibrium point. However, their control is difficult due to the uncertain, time-varying and nonlinear nature of the processes involved. In this paper we propose an adaptive control law that globally stabilizes the desired biomass set-point. Further, in a certain region of the state space the controller linearizes the dynamic behavior after some time scaling. This way, the orbits of the closed loop system are imposed by the designer. The intrinsic integral action of the gain adaptation rejects parameter uncertainties. Moreover, the controller implementation only assumes biomass concentration to be measured. Both simulated and experimental results show the performance of the controller.

Highlighted publication

 19-03-2018 "Global stabilisation of continuous bioreactors: tools for analysis and design of feeding laws", AutomaticaVolume 89March 2018, Pages 340-348

This work revisits the dynamic behaviour of stirred continuous reactors in which a single bioreaction with unknown kinetics occurs. Conditions on the feeding strategy to avoid washing out the biomass and falling in batch operation are obtained. These conditions derive in a closed positively invariant region including the desired operating point. It is stated that no closed orbits may exist in this region and, furthermore, that no fixed point exists but on one of its borders. Therefore, global stability is achieved by finding a feeding law that fulfills the aforementioned invariant conditions and gives a single equilibrium for a first-order dynamics. These results are useful to determine the stability properties of different control laws and, more importantly, to design new ones. The main advantages of the proposed approach are its simplicity and that, differing from previous results, input saturation does not affect stability results. The potentiality of the developed tools is illustrated by means of classical and novel feeding laws. 

Welcome to new PhD student

02/02/2018 Fernando Nobel Santos-Navarro has won a UPV PhD grant. 

F. Nobel Santos-Navarro has won a UPV PhD grant to develop the thesis Implementation of feedback control mechanisms for bioproduction optimization using gene synthetic circuits.

 

 

Seminar

28/09/2015 Dr. Sánchez Peña, principal investigator of the CONICET at the Technical Institut of Buenos Aires gives a seminar on September 28th 

Dr Sánchez Peña is a reknown expert in robust identification and control. In the last years he has become interested in the application of robust control techniques to artificial panchreas for treatment of diabetes type I. We will also be one of the members of the jury in the defense of Ana Revert's PhD thesis next Septembre 29th.

 

iGEM 2015 Jamboree

27/09/2015 Valencia_UPV team members are doing a great job at the iGEM 2015 Jamboree

Valencia_UPV team's project, AladDNA, is having a very good reception at the iGEM 2015 Jamboree. The project develops a light-based decoder that allows a plant seedling to express one out of a set of proteins encoded. 

The students are quickly learning to present and defend their project, and also had time to know some of the Synthetic Biology pioneers, like Tom Kinght.  Still waiting for the final presentation of the project we already can say that both the poster, and the great Minecraft application developed by the team, SynBioCraft, are a success. SynBioCraft is a game for learning synthetic biology, directed to people  at all ages and formative backgrounds. The game was presented during the special worshop on planst synthetic biology co-organised by Diego Orzaez, one of the team instructors.

Valencia_UPV igem 2015 team

 

Sexy Plant finalist and public prize at ClimateLaunchpad

15/09/2015 The Sexy Plant project gets the public's prize, and finalist among 800 projects at ClimateLaunchpad final in Amsterdam.

The Sexy Plant, a start-up originated from an idea presented by the UPV team to the IGEM competition last 2014,  uses synthetic biology as a means to creat plants producing insect pheromones as an alternative to pesticides in the fight against pests.

ClimateLaunch pad is the largest European competition on business ideas for clean technologies. It is promoted by Climate-Kic, and initiative of the European Union.

The start-up is composed by three young UPV students, Alfredo Quijano, Alba Rubert, and  Alejandra González. You can watch the Sexy Plant presentation at https://www.youtube.com/watch?v=BIa1GLkEI-w, and an interview to Alfredo Quijano at https://www.youtube.com/watch?v=Br_sE266KLI

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