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https://www.nwo-i.nl/nwo-domein-enw/onderzoeksprogrammas/vrije-programmas/nr-151-spatio-temporal-patterns-of-membrane-protein-activity/

Geprint op :
14 december 2018
15:19:23

Approved FOM programme

Number

151.

Title

Spatio-temporal patterns of membrane protein activity (PMP)

Executive organisational unit

BUW

Programme management

Prof.dr. P.R. ten Wolde

Duration

2014-2019

Cost estimate

M€ 2.3

The objective
The aim of this programme is twofold: to reconstitute a cellular system that combines protein signaling at the membrane with protein shuttling between the membrane and the cytoplasm via cytoskeletal filaments; to combine experiments with modelling to elucidate the spatial patterns of proteins that can be formed in this system.

Background, relevance and implementation
Many cellular processes, such as mating, budding, and differentiation, involve a complex interplay of pattern formation of proteins at the membrane and changes in cellular shape. Signaling proteins that form the pattern at the membrane are typically released into the cytoplasm and then recycled back to the membrane by motor proteins over the same cytoskeletal filaments that also drive cellular shape changes. This shuttling of proteins between the membrane and the cytoplasm creates a positive feedback loop between protein pattern formation, cytoskeletal organization, and cellular shape changes.

While the importance of the interplay between pattern formation, filament transport, and shape change is now increasingly being recognized, our understanding of these processes is still highly limited. The principal reason is that these processes are intrinsically difficult to study within the complexity of the living cell. The aim of this programme is therefore to reconstitute a cellular system in vitro, first in emulsion droplets and later in vesicles, that combines signalling with filament shuttling. Together with modelling, we will elucidate which patterns can be formed, and how these patterns steer shape transformations and vice versa.

The programme will be carried out by five groups with complementary expertise. Dogterom will bring in biophysical expertise to reconstitute the filament-based shuttling system; the biochemist Gadella is an expert in membrane-based signalling; the cell biologist Bastiaens will contribute expertise in the spatial design of the system; the chemist Danelon will be respon­sible for in situ protein expression and Ten Wolde will carry out the modelling.

It is increasingly recognized that diseases are not only caused by the malfunctioning of single biomolecules (e.g. proteins), but can also arise at the level of the network of interactions between these molecules. This recognition has driven the development of a new approach, called systems biology, which is now rapidly being adopted in industry. As such, our funda­mental investigations may lead to biomedical applications in the long term.

Remarks
The final evaluation will be based on the self-evaluation report initiated by the programme leader and is foreseen for 2019.

Please find a research highlight that was achieved in 2013 within this FOM programme here.