A novel systems analysis of a synaptic gene network
A novel systems analysis of a synaptic gene network
批准号:
10410170
负责人:
Rui Sousa-Neves
金额:
$25.0万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-09-30 至 2023-05-31
关键词:
3-DimensionalAddressAdministrative SupplementAffectAlzheimer&aposs DiseaseAmyloid beta-Protein PrecursorAutomationAwardBinding SitesBrainBrain imagingBrain regionCandidate Disease GeneCell DeathComplexConfocal MicroscopyConfusionDNA BindingDataDecision MakingDiagnosticDiseaseDisease MarkerDrosophila genusElderlyFemaleGene ExpressionGenesGeographic Information SystemsGoalsHealthHornsHumanHuman GenomeIndividualLabelLateralLeadLinkLobeMeasurementMembraneMemory LossMicroscopeModalityMolecularNeurodegenerative DisordersNeuronsOdorsParentsPopulationPredictive FactorProcessProteinsPublic HealthResearchResolutionRisk FactorsScanningSensorySeriesSpatial DistributionSpeedSynapsesSystemSystems Analysisapolipoprotein E-4cholinergicchromatin remodelingcognitive functioncostdetectorexperimental studyfamilial Alzheimer diseaseflygenetic variantgenome wide association studyimaging Segmentationimprovedinstrumentknock-downmalemultidimensional datanovelnovel therapeuticsolfactory lobepreventreceptorresponsesegregationstatisticstargeted treatmenttooltranscription factor
中文摘要
近几十年来,随着老年人口的增加,阿尔茨海默病(Alzheimer's disease, AD)的发病率越来越高
英文摘要
With the increase of the elderly population in recent decades, Alzheimer's disease (AD) is
quickly becoming a public health concern. The disease causes loss of memory, confusion and
affects decision-making. With the few exceptions of familial AD cases linked to APP and ApoE4
as a risk factor, most AD cases have unknown ethiology. Therefore, a major effort has been
directed to identify genes associated with AD with the goal of developing better diagnostic tools
and new therapies for the disease. The majority of the strategies to identify AD markers, targets,
predictors and risk factors still rely on Genome Wide Association Studies (GWAS), which are
known for high costs and a high rate of false positives. In contrast, our study starts with a
synaptic network of proteins required for decision-making in Drosophila, which is conserved in
flies and in humans. This synaptic network is composed of genes that have DNA binding sites of
DATI, a conserved transcription factor that allows female flies to either accept or reject males.
Remarkably, 88% of the genes in this network are present in the human genome and 100% of
these human genes also contain DATI binding sites, indicating that this is a very deeply
conserved gene network likely to be of significance to understand higher cognitive functions.
Consistent with this view, 10% of the proteins of the network interact with APP and 13% of the
genes listed in AGORA as candidates for AD are part of this network. Together, these data
make a strong case that this network is significant for understanding AD. In addition to
identifying these genes, this project seeks to understand how these genes lead to the
emergence of cognitive functions. To begin addressing this question, we have been using a
series of tools to analyze multidimensional data in 3D space in intact brains. These tools allow
us to analyze in fluorescently labeled neurons how the knockdown of a gene of the network
modifies the levels and localization of other genes of the network using Geographic Information
Systems. This administrative supplement request will partially support the acquisition of a new
instrument, the Zeiss LSM900 confocal microscope with Airyscan 2. To a significant extent, the
throughput of these analyses depends on the scanning speed of the confocal microscope, the
resolution required, the sensitivity and automation in the process. We expect that the acquisition
of this new compact confocal system will allow us to increase the throughput and resolution of
our analyses, ultimately increasing the impact of our study.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
A novel systems analysis a synaptic gene network
-
批准号:9791149
-
项目类别:
-
资助金额:$40.0万
-
财政年份:2018
-
负责人:Rui Sousa-Neves
-
依托单位:
A novel systems analysis a synaptic gene network
-
批准号:10432056
-
项目类别:
-
资助金额:$40.25万
-
财政年份:2018
-
负责人:Rui Sousa-Neves
-
依托单位:
A novel systems analysis a synaptic gene network
-
批准号:10188376
-
项目类别:
-
资助金额:$40.25万
-
财政年份:2018
-
负责人:Rui Sousa-Neves
-
依托单位:
海外基金