New method to determinate precise gene dosage

Quantitative Systems Biology

4 October 2017

A team of researchers lead by systems biologist Matteo Barberis (SILS, UvA) has envisioned an innovative method that allows the quantification of gene copy numbers in mammalian cells. Their findings have been published in the latest issue of Nature NPJ Systems Biology and Applications. A request for a patent has been submitted for the methodology.

The number of copies of a gene in a cell is reflected in the amount of protein produced. In turn, the assembly of individual proteins into functional, multi-protein complexes is fundamental to control the temporal decisions (also called switches) underlying all biological functions in living organisms. The aim of this study was to envision a methodology to quantify precisely protein dosage, as modulation of protein abundance and stoichiometry within complexes is critical to set the timing at which molecular switches occur.

Experimental strategy

The UvA researchers have conceived an experimental strategy, named Maximum Allowable mammalian Trade–Off–Weight (MAmTOW), that will allow measurement of the absolute protein concentration in vivo and will precisely determine protein dosage. The amount of protein affects the timing of cellular switches such those occurring in the cell cycle, i.e., the cellular process that allows to transfer the genetic material to the descendants and for their reproduction. The findings of the present study can help to understand the effect that protein abundance has on cell integrity.

Major breakthrough

Determination of precise gene dosage is a major breakthrough in Life Sciences. Traditional methods that investigate one molecule at a time are insufficient to understand how modulation of proteins within multi-protein complexes allows for: i) flexibility to respond timely to a variety of signals, while (ii) simultaneously guaranteeing cellular integrity. A systems biology approach where the MAmTOW method can be integrated with dedicated computer models helps to understand quantitative dynamics of signaling processes at the systems-level.

Publication details

Matteo Barberis and Paul Verbruggen: ‘Quantitative systems biology to decipher design principles of a dynamic cell cycle network: the “Maximum Allowable mammalian Trade–Off–Weight" (MAmTOW)’ in Nature NPJ Systems Biology and Applications, 19 September 2017

Published by  Swammerdam Institute