Free-living cells navigate a challenging world using solitary solutions. In contrast, cells within a multicellular organism must act as a collective to carry out functions for the benefit of all. We study the unique and complex biology of cells in the context of tissues and organs. Model organisms such as the fruit fly Drosophila provide an unprecedented opportunity to understand the cell biology of multicellularity. Our lab uses a variety of high-throughput experimental tools such as genomics, genetics and quantitative imaging. We couple such data-intensive experiments with computational analysis and modeling. The goal is to gain a comprehensive and predictive understanding of how multicellular properties emerge from the collective of cells present in a tissue or organ. Such understanding has implications for diseases such as cancer, as well as modern methods of tissue regeneration to treat disease.
NON-CODING RNAS AND DEVELOPMENT
A large portion of the RNA transcriptome is comprised of RNAs that do not code for proteins. These include siRNAs, miRNAs and lncRNAs. We use genomics and genetics to understand the molecular mechanisms by which non-coding RNAs function in Drosophila development. Currently, we are using CRISPR-based genome editing to ablate specific lncRNAs and study their roles in development.
METABOLISM AND ITS INTERACTION WITH GENE REGULATION
Gene expression is regulated by molecular activators and repressors. We have found the impact of such regulators is contingent upon the rate of cellular metabolism. The dynamics of gene expression are less dependent on gene regulators if metabolic rate is modestly slower. Currently, we are exploring this relationship and its potential impact on organismal aging.
POSITIONAL INFORMATION FOR CELLS IN A COMPLEX TISSUE
Tissues are composed of 10,000s of cells and yet each cell "learns" certain properties of the tissue such as its size and polarity. Cells stop dividing when the tissue reaches its optimal size; cells polarize along the plane of the tissue aligned to a major body axis. How do cells learn such facts? We study two protocadherins present in cells that somehow provide this information. The protocadherins are expressed in tissue-scale gradients that are key to their function.
REGULAR PATTERNING OF DIFFERENTIATED CELLS IN TISSUES
Many body systems have precisely ordered arrays of specialized cells to carry out system functions. We study the Drosophila eye as one such system. Its regular clusters of photoreceptors emerge from a traveling wave like a growing crystal. We have found this happens by a mechanochemical mechanism involving cell flows. Currently, we are performing single cell RNA sequencing (scRNA-seq) to follow the dynamics of gene expression as eye cells change their states.
NATURAL VARIATION AND EVOLUTION OF BODY FORM
We use a novel geometric method to detect variation in wing morphology due to natural genetic and environmental variation. Wing traits are constrained to a restricted and correlated "space" of phenotypes. We are currently determining if the evolution of wing form is also constrained within the same phenotype space. We hope to understand how morphology naturally evolves by this mapping of genotype to phenotype.