Master Thesis Project in Animal Cell Technology – Metabolic Flux Analysis Modeling in Chinese Hamster Ovary Cells
The cell technology group (CETEG) belongs to the KTH School of Biotechnology and the Division of Bioprocess Technology, with our clean labs and offices situated on floor 1 at the AlbaNova University Centre in Stockholm. We are now offering master thesis projects related to our research about metabolic flux analysis modeling of Chinese Hamster Ovary (CHO) cells.
CETEG group website: http://www.ceteg.se/
CHO cells are widely used
within the industry for production of biopharmaceuticals. These cells typically
demonstrate an inefficient metabolism with high consumption of medium carbon
sources and high production of toxic by-products. This metabolism is however
flexible. Varying environmental parameters, i.e. the nutrient availability, can
affect what metabolic pathways the cells use. Altering some of these parameters
could thus lead to a more efficient use of the medium components, with
increased flux towards biomass and product formation.
Metabolic flux analysis is a
mathematical approach that can be used to quantitatively investigate and model the
metabolism of cells. Utilizing this approach for modeling of mammalian cells is
however challenging due to the complexity of these organisms.
Our group has chosen to focus
on the amino acids in the growth medium and modeling of the amino acid and
energy metabolism. By conducting experiments we generate data that can be used
in metabolic flux analysis to provide deeper insight into what reactions the
cells use under varying experimental conditions. This is followed by computational
investigations using various assumptions and modeling strategies.
The master thesis will
consist of the following parts:
·
Literature study focusing on certain amino acids and
their metabolism
·
Design of a highly parallel small-scale culture
experiments
·
Execution of the experiments in our clean cell culture
laboratory
·
Analysis of metabolites (amino acid HPLC and
colorimetric enzymatic kit assays on multi-well plates)
·
Compiling the data and initial interpretation of the
results
·
Metabolic flux analysis and metabolic flux analysis
modeling using Matlab
·
Report writing and final presentation
We will accept up to two students, who will then
perform individual projects but benefit from collaboration in certain parts of
the workflow.
Ideal applicants are highly motivated MSc level
students from the field of biotechnology, bioengineering or similar. Experience
of Matlab is advantageous.
English is our working language since we are an
international team. Therefore, applicants need to have a proficient level of
English in speaking, reading and writing.
Questions and applications are sent to Erika Hagrot
at: hagrot@kth.se.
Apply by sending your CV/Résumé, course transcript and
a short motivational letter describing your background and interest for the
project.
Perfusion of Chinese
Hamster Ovary cell cultivation producing monoclonal antibody
The cultivation of Chinese Hamster Ovary cells, CHO, is
widely used in the biopharmaceutical industry for the production of drug
proteins. Perfusion is a mode of operation where a continuous replacement of
the conditioned medium by fresh medium is operated. It has the advantage of
allowing high cell densities and therefore increased higher product titres. This
mode of operations is also required for some instable proteins since it allows
the immediate storage of the cell-free supernatant containing the product of
interest at low temperature where the proteolysis is not active.
Our group has achieved up to 200x106 cells/mL
using a CHO cell line in perfusion, a world-record, and performed several
projects using different perfusion systems since the group started in 2008. The
purpose of the present work is to study a new perfusion system. Monoclonal
antibody producing CHO cell lines will be used for the investigation. This innovative
project is perfect for a student educated in bioprocess, highly motivated with technical
skill. The practical work will be performed at the Royal Institute of
Technology in Stockholm.
English is our working language since we are an
international team. Therefore, applicants need to have a proficient level of
English in speaking, reading and writing.
Questions and applications are sent to Veronique Chotteau,
chotteau@kth.se
Apply by sending your CV/Résumé, course transcript and a
short motivational letter describing your background and interest for the
project.