脂类占据人类大脑干重的一半左右，在大脑神经信号传导过程中发挥着重要的作用。最新的研究表明，脂类的异常可能导致一些常见认知性疾病。但是，目前对于人类大脑脂质组的组成以及变化却知之甚少。当前基于质谱的脂质组分析技术的发展，为大规模研究脂质组组成的差别以及不同脂类的分布创造了条件。在本项目中，基于优化的质谱脂质组测量技术，我们将研究正常人脑以及自闭症患者大脑在出生后各个发育阶段的脂类组成差异，以及研究相比于近人灵长类人脑特异的脂类组成成分，进而构建出世界上第一例完整地人脑脂质组图谱。同时，通过脂质组、转录组的整合，我们还将构建出脂质组在人脑发育各阶段动态变化的调控图谱，以及与人脑特异的脂类组成成分变化以及自闭症患者大脑脂类异常相关的关键调控元件。最终我们将能够为揭示人类大脑功能的正常行使以及自闭症患者大脑的异常提供新的分子理论基础，同时还能够完善我们对人类认知进化过程的认识。

Lipids make up half of the human brain in dry weight and play important roles in neuronal signaling. Hydrophobic properties of lipids determine the chemical structure, molecular shape and organization of neuronal and glial membranes and this way regulate vesicle fusion and ion fluxes, and create specialized microenvironments necessary for cellular communication. Further supporting important role of lipids in the brain functionality, disruptions of genes involved in lipid metabolism have been recently recognized as one of the key elements of most common human cognitive disorders. Despite importance of lipids in brain functionality, nothing is currently known about human brain lipidome composition and dynamics. Only recently the progress in mass spectrometry based lipidome analysis approaches has opened experimental opportunities for profiling large-scale differences in lipid composition as well as topographical distribution of individual lipid species. In this study, we aim to take advantage of such an optimized lipidome analysis approach developed at the Max Planck Institute for Molecular Plant Physiology (Germany) to conduct the first in-depth study of human brain lipidome, determine lipid composition dynamics in healthy and autistic humans during postnatal brain development, and identify human-specific lipidome features. The research will be based on the unique collection of developmental time-series samples from healthy and autistic humans, as well as non-human primates – chimpanzees and macaque – provided by our research collaborators: the Mount Sinai Hospital (USA) and the Max Planck Institute for Evolutionary Anthropology (Germany).In addition to the lipidome measurements, changes in genes expression across all samples will be monitored using RNA-sequencing (RNA-seq). Combination of lipidome and transcriptome measurements will allow us to reconstruct regulatory networks controlling lipidome developmental dynamics, its unique human-specific features, and lipid composition disruptions associated with autism, as well as identify key factors and elements of these networks. The sum of the state-of-the-art lipidome and transcriptome methodologies, unique tissue sample collection, and novel integrative data analysis algorithms combined within this study provide clear potential to deliver principally novel insights and breakthrough discoveries into the nature of mechanisms underlying human brain functionality and autistic dysfunction, as well as evolution of cognitive traits specific to humans.