In principio erat Lactococcus lactis: Towards a membrane protein overproducer host

Joao Paulo Coelho Pinto

Research output: ThesisThesis fully internal (DIV)

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It is probably universally known among the general public that DNA is the carrier of genetic information. What is less well recognized is the fact that DNA codes for proteins and that proteins are the major functional components in cells. Their functions can be as diverse as breaking starch in cereals into elementary sugars used for energy, acting as neuroreceptors guaranteeing the flow of information throughout the nervous system, or determining the curliness of hair.
Membrane-proteins can a.o. be found in the membranes separating the inner side of cells from the outside. They are very important, representing approximately 1/4 of all proteins of an organism, and are the targets of over 60% of current medicines. We need to know much more of how membrane-proteins work (or dis-function!), but until now they are rather rudimentarily characterized. This is because they are very difficult to isolate and purify in sufficient amounts to perform structure-function studies.
In this thesis, we establish the bacterium Lactococcus lactis as a “factory” for production of membrane-proteins. Because of the universality of the genetic (DNA) code we were able introduce the genes for several membrane-proteins in L. lactis and have the bacterium make these proteins. Thus, we have successfully improved the ability of L. lactis to produce, for example, the human membrane-protein PS1Δ9, which is linked to the susceptibility to Alzheimer, by more than 4 fold.
We also upgraded the “toolbox” for genetic modification of L. lactis and unraveled the gene expression biography of this organism, all of which will benefit many other research questions posed by the L. lactis scientific community.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Groningen
  • Kok, Jan, Supervisor
  • Poolman, Berend, Supervisor
Award date29-May-2015
Print ISBNs978-90-367-7799-5
Electronic ISBNs978-90-367-7798-8
Publication statusPublished - 2015

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