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Projects. Life and Earth Sciences

Epigenetic alterations in tetraploid neurones and Alzheimer's disease

Lead Researcher:
José María Frade López

Research Centre:
Instituto Cajal. CSIC. Madrid.

Synopsis: 

José María Frade LópezObjective 1: the establishment of a colony of Mapttm1(GFP)Klt/J mice in the animal facility of the Cajal Institute (months 1‑12).
During the first six months of the project a colony of Mapttm1(GFP)Klt/J mice was created in the animal facility of Cajal Institute, which now has two litters of these mice. These mice will be fundamental in the isolation of neurones, given that they were designed to express protein GFP in them.

Objective 2: the differentiating genomic analysis between diploid and tetraploid neurons (months 4‑12).
Optimisation has commenced on the procedure to separate diploid from tetraploid neurons, based on the brain tissue of adult mice (wild-type mice). The use of papain as the proteolytic agent aids the disassociation of cerebral cortex cells, which can be marked with DraQ5, a DNA marker that crosses the membrane and marks DNA in vivo. The aim is to use this method to isolate tetraploid neurons from Mapttm1(GFP)Klt/J mouse tissue that will then be used to analyse genetic expression using microarrays.

Objective 3: Analysis of the epigenetic mechanisms involved in the changes in genetic expression associated with neuronal tetraploidy (months 13‑36). This phase of the project has yet to start.

Objective 4: Analysis of the epigenetic mechanisms involved in the changes in genetic expression associated with AD (months 1‑36).
The expansion of APP/PS1 transgenic mice has commenced, which will be crossed with Mapttm1(GFP)Klt/J mice to obtain information on changes in genetic expression in the neurons of APP/PS1 mice.


Researcher's web address: 
http://www.cajal.csic.es/departamentos/frade-lopez/frade-lopez.html


José María Frade López

Graduate in Biology from Complutense University, Madrid, in 1989. He wrote his doctoral thesis at the Ramón y Cajal Institute (Superior Science Research Council, CSIC) on the influence of the proteins of the extracellular matrix on neuronal differentiation, and he was awarded his Doctorate by the Autonomous University, Madrid, in 1994. After a one-year postdoctoral stay in the laboratory of Dr. Rodríguez-Tébar in the Ramón y Cajal Institute, working on the effect of neurotrophins on neurogenesis and the apoptosis associated with neuronal differentiation, he moved to Germany in 1996. There he undertook a postdoctoral stay in the Neurobiochemistry Department of the Max-Planck Neurobiology Institute, directed by Professor Yves-A. Barde. During the two and a half years that he stayed there, Dr. Frade performed studies of the induction of neuronal apoptosis mediated by the NGF neurotrophin through its receptor p75NTR, and his work is now an obligatory reference in this subject. At the end of 1998, Dr. Frade returned to the Ramón y Cajal Institute with a Reincorporation Contract, where he continued his studies on apoptosis due to NGF and its relationship with the reactivation of the cell cycle of neurones in the process of differentiation. In August, 2000, Dr. Frade obtained a post of Tenured Scientist in the Ramón y Cajal Institute and in 2008 he was promoted to Scientific Researcher. His work currently centres on the study of the role of tetraploid neurones in the normal and pathological working of the brain. Dr. Frade is the author of more than 40 scientific publications, many of them in highly prestigious journals such as Nature, PNAS and Neurone, and has been cited almost two thousand times. He also holds two patents, and is a member of several international scientific associations.


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