Many people have `disease causing' mutations in their genomes but never actually develop a disease. Researchers from the Centre for Genomic Regulation (CRG) have studied how non-genetic variation in gene expression may help to predict whether an individual develops a disease or not.

The effects of a particular disease causing mutation can be very severe in some individuals, only mild in others, and of no consequence in a lucky few. These differences in the outcome of mutations are usually ascribed to interactions with additional variation (i.e. to genetics) or to interactions with lifestyle, diet etc (i.e. to the environment). However it has long been realised by researchers who work with laboratory animals that even in the absence of genetic variation - and even in a highly controlled laboratory environment - the same mutation can kill one individual and yet have no apparent effect in another. What are the causes of this variation in the effects of inherited mutations?

Researchers at the CRG have studied this question using the microscopic worm, Caenorhabditis elegans, as a model. Due to its simplicity, C. elegans is one of the most widely studied organisms in biology, and was the first animal to have its genome sequenced. Recently three different Nobel Prizes have been awarded for research using C. elegans. The researchers tested the idea that it is 'random' variation in gene expression (the extent to which a particular gene is turned on or off) during the development of the animal that influences the outcome of each mutation. They developed a method to quantify the activity of genes in developing embryos, allowing them to test the consequences of variation in the expression of particular genes. Using this approach they found that 'random' differences in the expression of a gene can sometimes have quite a big effect. Indeed, by quantifying variation in the expression of both a specific and a more general cellular component, it was possible to predict much more accurately what the consequences of a particular inherited mutation would be for a particular individual.

The work illustrates how, even if we completely understand all of the genes important for a particular human disease, we may never be able to accurately predict what will happen to each person from their genome sequence alone. Rather, to develop personalised and predictive medicine it will also be necessary to consider the varying extent to which genes are turned on or off in each person.

Since 2009, the Large Hadron Collider (LHC) at CERN (Geneva, Switzerland) collides protons at a center-of-mass energy of 7 TeV, the highest energy ever reached by a particle accelerator. One of the main goals of the LHC is the search for the Higgs boson, the last piece of the Standard Model that remains undiscovered. The so-called Higgs mechanism was introduced in 1964 to explain the breaking of the electroweak symmetry, leading to a massless photon, mediator of the electromagnetic force, and very heavy W and Z bosons, mediators of the weak interaction. The Higgs mechanism would also explain the mass of fermions as the Higgs field permeates the Universe and interacts with all particles endowing them with their mass. Finally, the existence of a Higgs boson associated with the Higgs field is postulated, although its mass is not predicted and must be determined experimentally.

During the last four decades, particle physicists have searched for the Higgs boson. In the 90's, the LEP electron-positron collider at CERN concluded that the Higgs boson, if it exists, should have a mass larger than 114.4 GeV at 95% confidence level (C.L). Since 2002, the quest for the Higgs boson was mainly undertaken by the CDF and D0 experiments at the 1.96 TeV proton-antiproton Tevatron collider at Fermilab (near Chicago, USA). The experiments were able to extend the excluded mass range at 95% C.L. to 156-177 GeV, still leaving much room for the Higgs boson to hide.

The analysis of the data delivered in 2011 by the LHC to the ATLAS and CMS experiments has translated into a huge step forward in the quest for the Higgs boson. In particular, the combination of searches at the ATLAS experiment has excluded at 95% C.L. the presence of a Higgs boson with mass in the ranges: 112.7-115.5 GeV, 131-237 GeV, and 251-453 GeV [1-4]. Most importantly, the experiment observes a suggestive excess of events around 126 GeV (see Fig. 1) which would be consistent with the potential signal of a Higgs boson, although the observation is not yet statistically significant. It corresponds to a 3.6 standard deviation from the background-only hypothesis (see Fig. 2) but, after including look-elsewhere effects, it translates into a 1% probability to be a simple background fluctuation.
In 2012 the LHC experiments will collect much more data, which should allow them to either discover the Higgs boson or completely exclude its existence. A. Juste and M. Martínez lead the analysis effort of the ATLAS data at IFAE, playing a central role in those channels whe