The Reilly Lab in Yale School of Medicine’s Department of Genetics (www.reilly-lab.com) is seeking postdoctoral researchers for funded projects to understand how genetic variants impact human health, evolution, and disease. We seek to answer a fundamental question remaining in biology: “how do genetic changes lead to functional changes at the molecular, cellular, and phenotypic level?”
We’re especially interested in understanding the role of non-coding cis-regulatory elements (CREs) in the genome, with a focus on variation within them. Genome-wide association studies have identified hundreds of thousands of genetic variants associated with human health and disease, but mechanistic traction has been limited. Similarly, natural selection is a powerful driver of human genetic variation between populations and may still impact modern traits or diseases (e.g. height, sickle cell anemia).
The Reilly lab develops and applies new high-throughput experimental approaches to interrogate the genome, such as non-coding CRISPR screens (Nature Genetics) and the Massively Parallel Reporter Assay (Cell, Science), as part of our work in an ENCODE functional characterization center (Nature Methods). Computationally, we also develop machine-learning approaches to predict the functions of these CRE perturbations. Together with these new tools, we use evolution as a powerful lens for characterizing genomic signals of positive selection that impact modern human phenotypes and diseases. As affiliates of the Impact of Genomic Variation on Function (IGVF) consortium, we collaborate at the national level on variant-to-function methods development, while offering access to a vast, cutting-edge scientific support network.
The lab has five main themes:
1. Genomic Technology: Developing new, large-scale experimental screens to perturb CREs.
2. Deciphering Regulatory “Grammar”: Using saturation mutagenesis and machine learning models to understand the “grammar” of how CREs regulate gene expression.
3. Interrogating Genetic Architectures: Through phenotype associations and network logic models, we explore how combinations of variants together create a phenotype or disease state.
4. Writing Novel Genome Function: Creating synthetic sequences that promote cell-type specificity of gene expression.
5. Exploring Evolution & Human Health: Bringing together the previous themes, we explore how changes in the non-coding genome affect questions of human health and the evolution of modern humans.
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