Atherosclerosis—a chronic inflammatory disease of the artery wall—is the underlying cause of human coronary heart diseases. Cells within atherosclerotic lesions are heterogeneous and dynamic. Their pathological features have been characterized by histology and flow cytometry and more recently, by bulk-tissue omics profiling. Despite this progress, our knowledge of cell types and their roles in atherogenesis remains incomplete because of masking of differences across cells when using genomic measurement at bulk level. Single-cell RNA sequencing (scRNA-seq) has catalyzed a revolution in understanding of cellular heterogeneity in organ systems and diseases. This project applies scRNA-seq to define the genetic influences on cell subpopulations and functions in atherosclerotic lesion of transgenic mice for candidate risk genes of human coronary heart diseases as inspired by human genomic discoveries. The students involved in this project are expected to work on: (1) analysis of scRNA-seq data using R/Bioconductor packages; (2) Interpretation of the data using pathway and network analysis. Some relevant workflows are available through the “Resources” page of our lab website at https://hanruizhang.github.io/zhanglab/.
Defective efferocytosis, the phagocytic clearance of apoptotic cells, by macrophages is the cause of many human diseases including tumor, autoimmune diseases and atherosclerosis. Enhancing efferocytosis has potential therapeutic benefits. Many key regulators of efferocytosis have been identified, but a systematic approach to map regulators of efferocytosis in an unbiased manner on a genome-wide scale is missing. This project applies innovative genome-wide CRISPR screen to discover novel regulators of macrophage efferocytosis.
A Fall 2018 internship is available in the Eaton lab to work on the development and application of machine learning approaches to historical evolutionary inference. Research will involve learning to use high performance distributed computing infrastructure, performing population genetic simulations, fitting machine learning models, and writing reproducible shareable code. The ideal candidate will have experience and interest in Python coding and a reasonable understanding of linear algebra.
DNA sequence reads from a community of microbial genomes are currently processed without considering sequence variants. The project involves building a processing pipeline of such billions of short reads, identifying closest strains they might belong to, assembling them into specific clones, calling their variants, and analyzing the dynamic nature of these bacterial strains along sampling points.