Role of insulin and insulin-like peptides in bone formation: identification of bone-specific target genes and regulatory mechanisms, and characterization of the insulin-mimetic effect of vanadium

Tese de Doutoramento em Biologia, Especialidade em Biologia Molecular, Universidade do Algarve, 2008

Study of influence of regulatory polymorphisms of expression in development of breast cancer

The human genome has millions of genetics variants that can affect gene expression. These variants are known as cis-regulatory variants and are responsible for intra-species phenotypic differences and individual susceptibility to disease. One of the diseases affected by cis-regulatory variants is breast cancer. Breast cancer is one of the most common cancers, with approximately 4500 new cases each year in Portugal. Breast cancer has many genes mutated and TP53 has been shown to be relevant for this disease. TP53 is one of the most commonly mutated genes in human cancer and it is involved in cell cycle regulation and apoptosis. Previous work by Maia et al has shown that TP53 has differential allelic expression (DAE), which suggests that this gene may be under the influence of cis-regulatory variants. Also, its DAE pattern is totally altered in breast tumours with normal copy number. We hypothesized that cis-regulatory variants affecting TP53 may have a role in breast cancer development and treatment. The present work aims to identify the cis-regulatory variants playing a role in TP53 expression, using in silico, in vitro and in vivo approaches. By bioinformatic tools we have identified candidate cis-regulatory variants and predicted the possible transcription factor binding sites that they affect. By EMSA we studied DNA-protein interactions in this region of TP53. The in silico analysis allowed us to identified three candidate cis-regulatory SNPs which may affect the binding of seven transcription factors. However, the EMSA experiments have not been conclusive and we have not yet confirmed whether any of the identified SNPs are associated with gene expression control of TP53. We will carry out further experiments to validate our findings.

Bycatch and discards of commercial trawl fisheries in the south coast of Portugal

Bycatch and discards are a cause of great concern in commercial world fisheries, with important ecological, economic and conservation implications. With the recent inclusion of a discards ban (‘landing obligation’), in the reform of the EU CFP, these issues have gained a tremendous attention from the economic, scientific, political and social point of view. Demersal trawl fisheries off the southern coast of Portugal capture an extraordinary diversity of species and generate considerable amounts of bycatch and discards. Bycatch includes commercially valuable target-species and bycatch species with low or no commercial value, but the great majority consists of unmarketable species, that are discarded. Bony fishes are dominant in bycatch and discards and the most discarded are of low or no commercial value. The reasons for discarding are fundamentally economic in nature (lack of commercial value) for bycatch species, and legal and administrative (legal minimum landing size) for commercially important species. The study of the reproductive biology of Galeus melastomus, discarded by crustacean trawls, suggests that a minimum landing size should be established for this species, and explains the importance of such a study in the assessment and management of fisheries. The discovery of a new species of the ray Neoraja iberica n. sp. contributes to the knowledge of the local marine biodiversity in Portuguese waters and of the global marine biodiversity. The three cases of abnormal hermaphroditism recorded in Etmopterus spinax, are the first cases known to date of hermaphroditism in this species. There is a need to find solutions to the problem of bycatch and discards of trawl fisheries in the Algarve coast. A combination of technical, regulatory and economic measures to minimize bycatch and reduce discards, before implementing a ‘landing obligation’, is thought to be the best approach to apply in the southern Portuguese multispecies trawl fisheries.