Mouse brain sections labeled for cortical neuronal subtypes (left) and glial subtype (right). Image credit: Omer Bayraktar
Our Research and Approach
The Cellular diversity of the human brain research group will start in August 2018.
We seek to explore the vast cellular diversity in the human body.
To understand human cellular diversity, we aim to (i) create single-cell level 3D maps of human organs using large-scale spatial transcriptomics and (ii) uncover the specialized functions of brain cell types using large-scale in vitro screens and mouse models.
We focus on studying neural cell type diversity in the human cerebral cortex.
Without the cerebral cortex, we would not have complex thought and behavior. The cortex also plays major roles in many neurodevelopmental and psychiatric disorders including autism spectrum disorders (ASDs) and schizophrenia. To precisely understand cortical function and determine how it goes awry in disease, we need to classify more than 16 billion neurons and 60 billion glial cells across this complex brain structure.
Our team will work on three major research directions:
Large-scale spatial transcriptomics for mapping human tissues: We will establish automated histology and imaging pipelines to map human tissues at single cell resolution at scale. We will use and develop highly-multiplexed single molecule fluorescent in situ hybridization (smFISH) methods to identify molecular cell types. We will extensively collaborate with Human Cell Atlas (HCA) and other teams at Sanger on diverse tissue applications and to develop automated image data analysis pipelines.
Cortical cell type diversity in health and disease: We will use single cell sequencing and large-scale spatial transcriptomics to map neuronal and glial subtypes in the developing and adult human cerebral cortex. We will further utilize spatial transcriptomics to identify cellular pathways involved in neurodevelopmental disorders such as ASD.
Large-scale screens to discover human glial function: Glia represent the majority of cells in the human cerebral cortex, but we know little about their biology. We will perform large-scale protein interaction screens and imaging-based cellular assays to discover glial molecular pathways that regulate neuronal development. We will also study glia-neuron interactions in vivo using mouse models. In our initial studies, we will focus on the role of human astrocytes in synapse development.
Research positions available
Postdoc, imaging specialist and PhD student positions available and will be posted on Sanger jobs soon. Please contact Omer (sanger email) if interested.
About Omer Bayraktar
Omer is fascinated by the cellular complexity of the brain. He is interested in using large-scale approaches to map brain cell types, to identify how glial cells shape neuronal circuits and to discover cellular pathways affected in neurodevelopmental disorders.
Omer is currently a postdoctoral fellow with David Rowitch at the University of California, San Francisco and the University of Cambridge. In August 2018, he will start his own group in the Cellular Genetics Programme at Sanger, where he will use large-scale spatial transcriptomics and functional screens to study human brain cellular diversity.
As a Life Sciences Research Foundation Fellow in David Rowitch’s lab, Omer developed a large-scale spatial transcriptomic pipeline to map single cell gene expression and neural subtypes in situ. Using this approach, he discovered the heterogeneity of astroglial cells across the layers and areas of the mammalian cerebral cortex. He identified that astrocyte layer patterns diverge from classical neuronal laminae, revealing the complex neuroglial architecture of the cerebral cortex.
Omer did his PhD with Chris Doe at HHMI to understand the developmental specification of neural diversity using Drosophila. He characterized a new neural stem cell model in the fruit fly brain that shares similarities with human neural stem cells. He discovered that multiple temporal patterning programs act in a combinatorial fashion to expand the neural diversity output of transit-amplifying progenitors. This work revealed a new concept in neural patterning that could expand neural cell type diversity in the human brain.
The International Human Cell Atlas initiative aims to create comprehensive reference maps of all human cells—the fundamental units of life—as a basis for both understanding human health and diagnosing, monitoring, and treating disease.
We explore the consequences of genome variation on human cell biology, and thus gene function in health and disease. We conduct large-scale systematic screens to discover the impact of naturally-occurring and engineered genome mutations in human iPS cells, their differentiated derivatives, and other cell types.
We measure, model, and modulate cell state. We use genome engineering and synthetic biology to create cell lines that can be employed for CRISPR/Cas9-based genetic screening and high throughput cell biology assays. We develop probabilistic models as well as software tools to accurately analyse the readouts.
The group seeks to elucidate the principles of protein structure evolution, higher order protein structure and protein folding, and the principles underlying protein complex formation and organization. We have a longstanding interest in understanding gene expression regulation, and in our wetlab at the Sanger Institute use mouse T helper cells as a model of cell differentiation.