Professor Pedro Ferreira

Abstract:

Alternative splicing is the mechanism by which different combinations of exons in the pre-mRNA give rise to distinct mature mRNAs. This process is mediated by splicing factors that bind the pre-mRNA and affect the recognition of its splicing signals. Saccharomyces species lack many of the regulatory factors present in metazoans. Accordingly, it is generally assumed that the amount of alternative splicing is limited. However, there is recent compelling evidence that yeast have functional alternative splicing, mainly in response to environmental conditions. We have previously shown that sequence and structure properties of the pre-mRNA could explain the selection of 3' splice sites (ss) in Saccharomyces cerevisiae. In this work, we extend our previous observations to build a computational classifier that explains most of the annotated 3'ss in the CDS and 5' UTR of this organism. Moreover, we show that the same rules can explain the selection of alternative 3'ss. Experimental validation of a number of predicted alternative 3'ss shows that their usage is low compared to annotated 3'ss. The majority of these alternative 3'ss introduce premature termination codons (PTCs), suggesting a role in expression regulation. Furthermore, a genome-wide analysis of the effect of temperature, followed by experimental validation, yields only a small number of changes, indicating that this type of regulation is not widespread. Our results are consistent with the presence of alternative 3'ss selection in yeast mediated by the pre-mRNA structure, which can be responsive to external cues, like temperature, and is possibly related to the control of gene expression.

Abstract:

This paper is concerned with string cosmology and the dynamics of multiple scalar fields in potentials that can become negative, and their features as (Early) Dark Energy models. Our point of departure is the "String Axiverse", a scenario that motivates the existence of cosmologically light axion fields as a generic consequence of string theory. We couple such an axion to its corresponding modulus. We give a detailed presentation of the rich cosmology of such a model, ranging from the setting of initial conditions on the fields during inflation, to the asymptotic future. We present some simplifying assumptions based on the fixing of the axion decay constant $f_a$, and on the effective field theory when the modulus trajectory is adiabatic, and find the conditions under which these assumptions break down. As a by-product of our analysis, we find that relaxing the assumption of fixed $f_a$ leads to the appearance of a new meta-stable de-Sitter region for the modulus without the need for uplifting by an additional constant. A dynamical systems analysis reveals the existence of many fixed point attractors, repellers and saddle points, which we analyse in detail. We also provide geometric interpretations of the phase space. The fixed points can be used to bound the couplings in the model. A systematic scan of certain regions of parameter space reveals that the future evolution of the universe in this model can be rich, containing multiple epochs of accelerated expansion.

Abstract:

In this paper we consider an extension to Eddington's proposal for the gravitational action. We study tensor perturbations of a homogeneous and isotropic space-time in the Eddington regime, where modifications to Einstein gravity are strong. We find that the tensor mode is linearly unstable deep in the Eddington regime and discuss its cosmological implications.