Observing live gene expression in the body

Most of our physiological functions fluctuate throughout the day. They are coordinated by a central clock in the brain and by local oscillators, present in virtually every cell. Many molecular gearwheels of this internal clock have been described by Ueli Schibler, professor at the Faculty of Science of the University of Geneva (UNIGE), Switzerland.

To study how the central clock synchronizes subordinate oscillators, the researcher's group used a variety of genetic and developed in collaboration with a team of UNIGE . In this way, the scientists were able to directly observe the bioluminescence emitted by 'clock genes' in mice for several months. This is applicable to numerous sectors of , which attracted the attention of the editors from the journal Genes & Development.

In mammals, there are many behaviors and biological functions that are regulated by internal clocks. Most of our cells have one, made from a family of 'clock genes', whose cyclic activity reaches a specific peak in 24 hours. These local oscillators are synchronized by a central 'pacemaker' in the brain which adjusts to light.

The firefly lights the way

The use of genetic engineering techniques enabled the study of molecular mechanisms that activate clock genes directly in cultured mammalian cells: 'We have coupled several of these genes to that of luciferase, the enzyme used by the female firefly for producing green light to attract males,' explained Ueli Schibler, member of the National Research Center Frontiers in Genetics. When a specific clock gene is activated in a cell that was transformed in this way, the light signal emitted can be measured using a highly sensitive bioluminescence detector. However, this device, which is capable of detecting signals on the order of a few photons, cannot be used for studying whole organisms. The contribution of André Liani's mechanical workshop, along with Jean-Pierre Wolf's and Luigi Bonacina's teams from UNIGE's Group of Applied Physics, was thus essential. These scientists developed a customized device that can accommodate mice for several months: 'We equipped it with reflective walls to deflect photons toward a highly sensitive photomultiplier tube to capture ,' says André Liani.

Follow the daily expression of clock genes live…

In collaboration with the University of Ulm and the Center for Integrative Genomics (CIG) of Lausanne, the biologists studied how the central clock synchronizes subordinate oscillators in mice. Various , coupled with the luciferase gene for light emission, were inserted into liver cells using a molecular vector. The time these rodents spent in the bioluminescent device allowed to demonstrate that the central clock generates signals, some of which act directly on the liver , and others which synchronize them indirectly by controlling the cycles of food intake.

…or the effect of a medication in mice

'This technology enables a drastic reduction in the number of needed for this type of experiment, and furthermore, it is applicable to many areas of biomedical research,' says Camille Saini, researcher in the Department of Molecular Biology at UNIGE and first author of this article. These complementary genetic and engineering technology tools could be used to directly follow certain biochemical effects of metabolites like cholesterol or glucose, as well as the response to potential treatments of diseases such as hypercholesterolemia or diabetes. Monitoring the response to various hormones, neurotransmitters and other biochemical messengers is also part of this application range.

add to favorites email to friend print save as pdf

Related Stories

How does body temperature reset the biological clock?

Aug 23, 2012

Numerous processes in our body fluctuate in a regular pattern during the day. These circadian (or daily) variations can be driven by local oscillators present within our cells or by systemic signals controlled by the master ...

At the heart of the circadian clock

Jun 11, 2013

(Phys.org) —Cellular processes in most organisms are regulated by an internal clock, and proteins called cryptochromes are at the core of its central oscillator. The three dimensional structures of cryptochromes ...

Recommended for you

Refining the language for chromosomes

Apr 17, 2014

When talking about genetic abnormalities at the DNA level that occur when chromosomes swap, delete or add parts, there is an evolving communication gap both in the science and medical worlds, leading to inconsistencies in ...

Down's chromosome cause genome-wide disruption

Apr 16, 2014

The extra copy of Chromosome 21 that causes Down's syndrome throws a spanner into the workings of all the other chromosomes as well, said a study published Wednesday that surprised its authors.

User comments