Nuclear receptors require co-activator binding in order to activate gene transcription. Ligand-induced nuclear receptor conformational changes facilitate the recruitment of certain co-activators through the recognition of a specific motif contained within the co-activator protein. Prof. Malcolm Parker ™s studies, funded by Cancer Research UK, identified this motif within the co-activator protein known as the LXXLL motif (where L is Leucine and X is any amino acid).

The nuclear receptor family represents a plethora of therapeutic targets for many clinical conditions. AstraZeneca ™s research interests initially will focus on the area of respiratory and inflammation; however, broader application is possible across all of the company ™s research areas. Targeting the nuclear receptor/co-activator interaction represents an alternative strategy for the inhibition of nuclear receptors.

cancertechnology/

The research undertaken at the Pediatr?­cs Laboratory aimed to test the efficacy of the micronuclei technique in detecting instability. The development of this technology has not been an easy task, and involved working jointly with the CIFA Toxicology Department at the University of Navarre. Specifically, Marta Zalaca?­n had to carry out a great number of trials in order to test and validate the technique and see how the numbers of micronuclei changed while we increased the benzoapyrene in vitro. In a preliminary manner we found that the micronuclei numbers in vivo increased in samples of those mothers who actively smoked during gestation; nonetheless, these results have to be interpreted with precaution, given that the placentary barrier has to be taken into account and so it can never be known with exactitude how much benzoapyrene is being transmitted to the foetus.

Apart from benzoapyrene, the research group has studied other genetic markers that tell us about tobacco habits, such as the status of mutation of the TP53 gene and the detoxifying enzymes of phase I and II drugs. There are enzymes involved in detoxifying the organism which are more or less efficient in various individuals presenting genetic polymorphisms. We are currently looking at the genotype presented in these samples.

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