Biennial Report 2005-2007 - Saha Institute of Nuclear Physics

200 Biennial Report 2005-07normal chromosomes varied from 14-28 (17.4 2.44), while these values varied from 36-83 (45.646.6) on the chromosomes with expanded allele. Result revealed that the frequency of deletion alleleat codon 2642 with expanded CAG repeat was significantly higher (20%) than that obtained amongthe normal chromosomes (5.8%). Besides, at D4S127 locus, the allele containing 32 dinucleotiderepeats was significantly higher among the expanded alleles (75.8%) compared to that obtainedamong normal chromosomes (44.2%). Among the major haplotypes, haplotype ‘31/G/7/A/+’,‘29/G/7/A/+’ and ‘31/G/7/A/-’ were significantly higher in the expanded chromosomes.Utpal Basu, Saikat Mukhopadhyay, Nitai P BhattacharyyaC&MB6.1.1.6 Study of AICD-adaptor interaction in Alzheimer’s Disease cell modelThe key protein involved in Alzheimer’s Disease (AD) pathogenesis is the Amyloid Precursor Protein(APP). One of the proteolytically cleaved products of this protein gives rise to Aβ peptidesthat in turn form senile plaques in the AD brain. The other product is the cytoplasmic domain ofthe protein, known as AICD. This domain contains conserved motifs that can act as a docking sitefor a number of adaptor proteins present in the cytosol. In order to investigate the effects of theseinteractions in terms of AD pathogenesis, we have cloned wild type AICD and its 5 mutant forms(the mutations reside in the functionally active motifs) both in bacterial and mammalian expressionvectors. We have cloned some of its adaptors such as Grb2, RasV1, SOS, Fe65 and Tip60. Now weare concentrating on viewing the interactions in vivo by confocal microscopy and in vitro by pulldown assays. At the genomic level recently we have started acquiring microarray data to assess thealteration in gene expression profile in neuronal cells in presence of excess amounts of AICD andits mutants.Mithu Raychaudhury, Debashis MukhopadhyaySG6.1.1.7 Evolutionary Characterization of Hippi-pDEDThe work related to structural and functional characterization of HIPPI revealed a novel DNAbindingproperty of the pDED domain of the protein. Importance of a few surface residues, predictedto be important in DNA binding, was validated experimentally. The phylogenetic historyof this gain of function was traced using Bioinformatics tools and DAPIN proteins were found tobe the most ancestral among the superfamily members. Results show that this is an independentgain of function unlike that of DEDD proteins.Aditi Moulik†, Pritha Majumder, Manisha Banerjee, Nitai P Bhattacharyya, Debashis MukhopadhyaySG6.1.1.8 Role of Intrinsically Unstructured Proteins (IUP) in Neurodegenerative disordersStructural and Biophysical characterization of HypK revealed it to be an Intrinsically UnstructuredProtein. Subsequently it was seen that majority of the proteins involved in complex disorders like