PEC12-25 CAPEC-PROCESS Industrial Consortium ... - DTU Orbit

Albert Emili Cervera Padrell
(ACP)
PROCESS
Supervisors: KVG
Chiara Piccolo (ChP)
CAPEC
Supervisors: RaG, P Piccione
(Syngenta)
Start: 01-04-2010; End: 31-03-2012
Sascha Sansonetti (SSA)
Heterogeneous microbial populations: modeling
distributions of protein production rate and plasmid copy
numbers in E. coli
Often the production of heterologous proteins in bacterial
hosts relies on the expression of multi-copy plasmids. The
productivity is, in these cases, closely correlated to plasmid
stability. Although a selective marker (e.g. antibiotic) is
typically present allowing for the selection of plasmidbearing
cells, the distributions of plasmid copy numbers
within the population vary. This reflects a trade-off between
the protein production and the growth rate.
This project aims at exploring modeling techniques to further
understand the dynamics of cellular distributed properties
under different growth conditions. The production of green
fluorescence protein (GFP) in E. coli is used as case study.
Starting from an unstructured kinetic model describing the
growth of E. coli, and increasing the model complexity, steps
will be taken towards the development of a population
balance model (PBM). This PBM should describe the
distribution of protein (and production rates) for cells
presenting different plasmid copy numbers, under varying
substrate availability. Tools such as parameter estimation
routines, numerical solvers for ordinary differential
equations, and discretization techniques for partial
differential equations will be explored in the formulation,
implementation and solution of the mentioned models.
Prediction of phase equilibria involving phase transfer
catalysis
Phase transfer catalysis (PTC) has the potential to stand out
as an attractive alternative to conventional processes for the
synthesize of special organic chemicals, from two immiscible
reactants, that normally will not contact each other: in PTC
systems a phase transfer catalyst acts as a shuttle between a
polar phase that contains the salt reactants and a non-polar
phase that contains the organic reactants. Many factors affect
PTC processes, for example, choice of the organic phase,
choice of the catalyst, presence of extra ionic species,
temperature, stirring rate. The aim of this project is to enable
semi-quantitative and quantitative estimations of phase
equilibria involving PTC and, ultimately, to develop a
systematic methodology to select the best system features and
operating conditions for a given synthesis
Research area: A; B; C
The rational selection of lipids for pharmaceutical
formulation
Lipidic dose forms are applicable to both the early and late
stages of product development in the pharmaceutical
industry. They are most frequently used to formulate Active
Pharmaceutical Ingredients (API’s) with inherently poor
27