Bayraktar Group

Cellular Genomics

We seek to explore the vast cellular diversity in the human brain using large-scale spatial transcriptomics, imaging and functional screens.

We seek to explore the vast cellular diversity in the human body.

To understand human cellular diversity, we aim to

1. create single-cell level 3D maps of human organs using large-scale spatial transcriptomics and
2. 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.

Top: Large scale spatial transcriptomic pipeline. Bottom: Mapping neuronal subtypes across cortical layer and areas in the mouse brain at single cell resolution in situ.

Research directions

Our team will work on three major research directions:

1. 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.
2. 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.
3. 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.