Transcriptome project: large scale gene expression analysis using DNA-Arrays
Transcriptome determination of the pancreatic islets from rats with maternal Diabe...
| Grant number: | 08/56594-8 |
| Support Opportunities: | Research Projects - Thematic Grants |
| Duration: | September 01, 2009 - August 31, 2013 |
| Field of knowledge: | Biological Sciences - Immunology - Immunogenetics |
| Principal Investigator: | Geraldo Aleixo da Silva Passos Júnior |
| Grantee: | Geraldo Aleixo da Silva Passos Júnior |
| Host Institution: | Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
| Pesquisadores principais: | Eduardo Antônio Donadi ; Elza Tiemi Sakamoto Hojo |
| Associated scholarship(s): | 11/10498-0 - Control of the transcriptome in Diabetes Mellitus,
BP.TT 10/12069-7 - Gene expression profiles and possible interactions between microRNAs and mRNAs in type 1 Diabetes Mellitus, focusing on response to oxidative stress and DNA repair, BP.DR |
Abstract
Molecular genetic studies will be performed on type-1 (T1-D), type-2 (T2-D) and gestational (GD) diabetes, evaluating the large scale gene expression profiles (transcriptome level). T1-D is an autoimmune disorder caused by the immunological destruction of pancreatic β- cells, leading to insulin dependence. Although several susceptibility loci have been described in association with T1-D, the major genetic component has been associated with MHC located at chromosome 6 (HLA) in humans and 17 in mouse. A counterpart of T1-D in experimental models has been reproduced in the non obese mouse (NOD), in which syntenic regions mouse/human have been described. T2-D and GD are characterized by glucose homeostasis unbalance primarily determined by environmental factors, including diet and life style in T2-0, predisposing to obesity (non-autoimmune diabetes), or during pregnancy (GD). Overall, these diseases reflect the contribution of genetic and environmental factors. According to our hypothesis, the study of distinct presentation forms of diabetes mellitus may answer questions about autoimmunity molecular genetics (T1-D), as well as questions referring to the consequences of metabolic alterations (T2-D and GD). The susceptibility loci of these complex diseases, including T1-D and T2-D, have been identified on the basis of linkage studies, which allow the association of specific chromosome regions with particular phenotypes. Therefore, several questions were addressed: firstly, whether such chromosome regions are in fact transcribed into mRNAs. Our approach to this subject relies on functional genomics, by using the microarray technology and bioinformatic analysis. This kind of approach may explore gene expression profiles at large scale encompassing several reported and unreported diabetes mellitus susceptibility regions. In addition, the meta-analysis of gene expression data may identify shared modulated genes in the three variants of diabetes. Secondly, whether or not gene expression profiles in humans may exhibit syntheny with those observed in mouse. To reach this goal, we will study NOD (non obese diabetic) mouse that reproduces T1-D, attempting to establish a parallel between human and mouse gene expression profiles relatively to susceptibility chromosome regions. Thirdly, evaluate regulators of gene expression that has been reported to be associated with autoimmune disorders, including the autoimmune regulator gene Aire (autoimmune regulatory in the context of T1-D and NOD; the consequences of the modulation of Aire expression will be studied using the RNAi (interference RNA) strategy. The regulatory role of microRNAs will further be studied in the context of T1-D, T2-D and GD. Finally, considering that the glucose metabolism is impAired in diabetes, yielding reactive oxygen species, gene expression profiles exhibited by the T1-D, T2-D and GD will be studied in response to the oxidative stress. In addition, for some particular genes, the effects of oxidative agents, including glucose and hydrogen peroxide, will be evaluated in terms of transcription (mRNA) and translation (protein) in lymphocytes obtained from healthy individuals. This approach may permit the validation of the microarray data. (AU)
| Articles published in Agência FAPESP Newsletter about the research grant: |
| More itemsLess items |
| TITULO |
| Articles published in other media outlets ( ): |
| More itemsLess items |
| VEICULO: TITULO (DATA) |
| VEICULO: TITULO (DATA) |