A regulatory approach to immune responses
The immune response can be described as a series of changes in gene expression that occur in a coordinated program across cells and tissues. The overarching goal of the lab is to build a gene regulatory network (GRN) model that describes the system-wide immune response in the sea urchin larva. Sea urchin embryos are the pioneering model system in regulatory biology. We have adapted the experimental techniques originally optimized for disentangling developmental GRNs (e.g., transgenesis and perturbation strategies) as well as cutting-edge single-cell sequencing to assemble the networks that control the larval response to pathogenic bacteria.
Characterizing hematopoiesis in sea urchin larvae
Like most echinoderms, sea urchins have a biphasic lifecycle that includes a relatively long-lived, feeding, free-swimming larval stage. Immune responses in larvae are mediated by a heterogeneous suite of cells that either 1) exhibit surveillance behavior; 2) can phagoytose foreign particles; or 3) express genes with immune-related functions. Larval immune cells are derived from a small subset of non-skeletogenic mesodermal (NSM) precursors that are patterned in early embryogenesis. Using transgenic perturbation and fluorescent in situ hybridization, we are working to define the GRN that mediates the transition from NSM to terminally differentated immune cells.
An evolutionary perspective on animal immunity
By protecting the host from harmful pathogens and cultivating a beneficial microbiota, immune systems operate at the forefront of animal evolution. In response to rapidly evolving microbes, animals rely on sophisticated mechanisms for detecting and eliminating pathogens. These mechanisms are intertwined with host mechanisms for maintaining cellular homeostasis and resolving stress. As the interface between conserved host mechanisms and rapidly evolving microbes, immune systems must balance these opposing selective pressures. Using comparative genomics, we are working to 1) identify fundamental, conserved principles of animal immunity; and 2) novel mechanisms for generating immunological diversity.
Environmental influences on the epigenome
As marine invertebrates, sea urchins are particularly susceptible to changing climates. The epigenome is emerging as one potential mechanism that allows organisms to respond to rapidly changing environments. In collaboration with Dr. Marie Strader (Texas A&M), the aims of this NSF-funded work are to 1) define how environmental conditions during embryogenesis shape the subsequent epigenomic landscape in larvae; and 2) link specific epigenetic changes with larval phenotypes related to the immune response.
A role for copper in embryogenesis
Copper is an essential micronutrient that is involved several fundamental aspects of cell biology, including electron transport, and protection from reactive oxygen species. Recent evidence has also implicated copper in metalloallostery (in which metals regulate enzyme activity by binding to an allosteric, rather than the active, site) and cuproptosis (a novel mechanism of programmed cell death). Using immunohistochemistry, protein biochemistry and phylogenetically-informed mutagenesis, we are working to identify potential roles for these two copper-mediated processes during the course of sea urchin embryogenesis.
Mucus provides a first-line of immunological defense for cnidarians
Most adult cnidarians produce a copious amount of mucus, a viscous secretion that is rich in carbohydrates, glycoproteins and salts. Although mucus has long been implicated in facilitating animal feeding, recent studies suggest that it may also provide a unique ecological niche for the host microbiome. We have been working to characterize the bacterial species present within the mucus of the the corallimorpharian Florida false coral (Ricordea florida). This work includes identifying potential host molecules involved in regulating these microbial communities.
Understanding the upside-down jellyfish, Cassiopea
In the face of a changing climate, many cnidarian species are threatened. In contrast, Cassiopea sp. are thriving and even increasing their range. While there are many potential mechanisms to explain this resilience, we are currently investigating two aspects of Cassiopea biology. First, in response to temperature stress, individuals exhibit plasticity in their rates of bell pulsation. Bell pulsation may promote water flow, which facilitates oxygenation and feeding. Second, we find that individuals with more blue pigment survive to higher temperatures. We are currently investigating the molecular bases underlying these observations.