Being at the right place at the right time

I am tremendously honored to receive the 2012 Women in Cell Biology Junior Award. In this essay, I recount my career path over the past 15 years. Although many details are specific to my own experiences, I hope that some generalizations can be made to encourage more women to pursue independent scientific careers. Mine is a story of choosing a captivating question, making the most of your opportunities, and finding a balance with life outside the lab.It is a great honor to have been awarded the 2012 Women in Cell Biology Junior Award from the ASCB. Looking back at the 15 years I have spent doing research in cell biology, my overwhelming feeling is that it has been and still is a lot of fun. I am extremely fortunate to have a job that I truly enjoy and that gives me complete intellectual freedom. My lab choices over the years were motivated by scientific curiosity and enthusiasm for new environments and topics, rather than by career building. It is thus truly amazing to be rewarded for (rather a lot of) work enjoyed.     

Being in the right location at the right time

Taking each coding sequence from the human genome in turn and identifying the subcellular localization of the corresponding protein would be a significant contribution to understanding the function of each of these genes and to deciphering functional networks. This article highlights current approaches aimed at achieving this goal.     

To be at the right place at the right time

Diagnosing Alzheimer's disease through MRI neuroimaging biomarkers has been used as a complementary marker for traditional clinical markers to improve diagnostic accuracy and also help in developing new pharmacotherapeutic trials. It has been revealed that longitudinal analysis of the whole brain atrophy has the power of discriminating Alzheimer's disease and elderly normal controls. In this work, effect of involving intermediate atrophy rates and impact of using uncorrelated principal components of these features instead of original ones on discriminating normal controls and Alzheimer's disease subjects, is inspected. In fact, linear discriminative analysis of atrophy rates is used to classify subjects into Alzheimer's disease and controls. Leave-one-out cross-validation has been adopted to evaluate the generalization rate of the classifier along with its memorization. Results show that incorporating uncorrelated version of intermediate features leads to the same memorization performance as the original ones but higher generalization rate. As a conclusion, it is revealed that in a longitudinal study, using intermediate MRI scans and transferring them to an uncorrelated feature space can improve diagnostic accuracy.     

MAPK signal specificity: the right place at the right time

Although the mechanisms that lead to activation of the Ras, extracellular-signal-regulated kinase mitogen-activated protein kinase (Ras/ERK-MAPK) signaling pathway have been studied intensively, the fundamental principles that determine how activation of ERK signaling can result in distinct biological outcomes have only recently received attention. Factors such as cell-surface receptor density, expression of scaffolding proteins, the surrounding extracellular matrix, and the interplay between kinases and phosphatases modulate the strength and duration of ERK signaling. Furthermore, the spatial distribution and temporal qualities of ERK can markedly alter the qualitative and quantitative features of downstream signaling to immediate early genes (IEG) and the expression of IEG-encoded protein products. As a result, IEG products provide a molecular interpretation of ERK dynamics, enabling the cell to program an appropriate biological response.     

Diversification rate shifts in the Cape Floristic Region: The right traits in the right place at the right time

Species diversity patterns are the product of diversification rate variation, but the factors influencing changes in diversification rates are poorly known. Radiation is thought to be the result of ecological opportunity: the right traits in the right environment at the right time. We test this in the Cape Floristic Region (CFR) of South Africa, in which pyrophytic heathland (fynbos) and non-pyrophytic Afromontane forest occur interdigitated. We infer transitions from forest to fynbos in three Cape clades (Penaeaceae, Phyliceae and Diosmeae) and test if they are associated with diversification rate shifts and the evolution of functional traits linked to fire, high insolation and seasonal drought. We estimate diversification rate shifts using maximum likelihood and use phylogenetic comparative methods to show that forest to fynbos shifts were associated with decreases in leaf area and specific leaf area and preceded or coincided with increases in diversification rates. Furthermore, we show that Penaeaceae, Phyliceae and Diosmeae species are typical members of their vegetation types in terms of their traits. The diversification rate shifts of Penaeaceae and Phyliceae are dated to the Miocene, when postulated aridification-driven changes in the CFR fire regimes may have triggered expansion of the fynbos at the cost of forest, providing an ecological opportunity for the diversification of fynbos lineages.     

Making the right moves

The structure of the nucleotide-free F(1)-ATPase from a thermoalkaliphilic bacterium presented in this issue of Structure (Stocker et al., 2007) reveals the structural interactions that prevent the enzyme from operating naturally in the hydrolytic direction. The data provide new insights into the mechanism of the F(o)F(1)-ATP synthase.