We develop cutting-edge single-cell technologies to dissect the molecular mechanisms that create cell-to-cell variability and drive individual cell behavior and collective function.
The heterogeneity of cells is a remarkable feature of the biological world. Understanding the origins and consequences of this heterogeneity represents a challenging task, yet it offers untapped opportunities for discovering new biological mechanisms, useful therapeutics and bioproducts. The technological advances in single-cell -omics field have enabled researchers to tackle cellular heterogeneity and discover new cell types in human body, recapitulate tumorigenesis process, and to build cell atlases of human organs. Over the years we learned that phenotypic outcome is not a static result of an encoded genome function alone but rather a dynamic state integrating various internal and external signals. In this process the cell transcriptome and epigenome serve as a much more accurate and exquisitely sensitive systems that integrates the functional readout of genome. Therefore, our research efforts stem from the assumption that phenotypic output and biological functions of heterogenous populations can only be understood from multi-omics characterization at single-cell level.
We have recently reported a novel high-throughput single-cell technology based on semi-permeable capsules (SPCs) [1, 2]. The SPCs are monodisperse liquid droplets surrounded by a thin shell permeable to biomolecules and proteins, yet impermeable to DNA/RNA molecules longer than 200 bp. As a result, cellular mRNA or gDNA molecules encoded by single cells are efficiently retained, while enabling complex molecular biology workflows on encapsulated cells and biomolecules by simply changing the reaction in which the SPCs are dispersed. The SPCs are resilient to various solvents, chemicals, freezing and heating making it well suited to process even the most challenging samples.
In the most recent study [3], we applied SPC-based scRNA-seq on whole blood extracted from acute myeloid leukemia (AML) patients allowing us to profile even the most fragile cells. The comprehensive characterization of cellular heterogeneity in AML allowed us to uncover a shared dysfunctional, stem-like state in the mature innate immune cell compartment, including granulocytes. In another collaborative study [4] with Atrandi Biosciences and Bigelow Laboratories (USA) we developed Environmental Micro-Compartment Genomics (EMCG) approach for high-throughput, quantitative genome sequencing of individual cells and extracellular genetic elements in environmental samples. By applying coastal seawater sample of 0.3 µl we obtained over 2,000 single amplified genomes corresponding to a broad range of cellular and extracellular entities of marine communities.
At Umeå University, I am seeking to further expand SPC-based applications in microbiology and biomedicine fields. Cellular heterogeneity is the defining feature of virtually any biological system, and our approach is to provide unprecedented functional and molecular resolution to this complexity. By identifying and characterizing low-abundance members in the heterogenous population (e.g., drivers of pathogenesis, persisters, unique drug-resistant tumor clones), we can learn much deeper about fundamental biology that govern human health and intervene in processes that drive complex disease states.