In the Whiteley Lab, we are interested in the social lives of bacteria. Currently, we are utilizing new technologies combined with classical genetic techniques to address questions about microbial physiology, ecology, virulence, and evolution. In particular, we are working on tackling the following questions:
1. How do bacteria communicate?
2. How do polymicrobial interactions impact physiology and virulence?
3. What is the role of spatial structure in bacterial infections?
4. How does the host environment impact microbial physiology?
We are interested in how ecology and evolution shapes cooperation, cheating and signaling (quorum sensing) in microbial populations, and the implications of this for the evolution of virulence and antibiotic resistance during infection. Our emphasis is on chronic infections such as those found in cystic fibrosis lungs, diabetic ulcers and non-healing wounds.
The Cognitive Motor Control Laboratory seeks to understand neurophysiology guiding skillful human-object interactions in upper extremity motor control. We use neuroimaging to identify anatomical and physiological circuits in humans that guide successful skilled behavior. Our clinical studies consider neural systems that can suffer injury or dysfunction related to deficits in skillful motor control, and how to utilize surrogate neural circuits in restorative motor therapies in stroke and upper limb amputation.
We seek to answer how animal behavior is set up by the collective behaviors of individual cells, over the entire course of brain and spinal cord development. We want to understand how gene activity can instruct developing neurons to move around, change shape, and connect to other cells. To do this, we study the simple larval nervous system of our closest invertebrate relatives, the tunicates. Tunicates, like us, belong to the Chordate phylum, but have very simple embryos and compact genomes. The laboratory model tunicate Ciona has only 177 neurons and is the only chordate with a fully mapped "connectome". We take advantage of this simplicity to understand molecular mechanisms that may underlie human neurodevelopment.
The work in this laboratory is focused on mechanisms underlying motor coordination in mammalian systems. These mechanisms are to be found in the structure and dynamic properties of the musculoskeletal system as well as in the organization of neuronal circuits in the central nervous system. Our work concerns the interactions between the musculoskeletal system and spinal cord that give rise to normal and abnormal movement and posture, and in the manner in which central pattern-generating networks are modified for specific motor tasks. Our studies have applications in several movement disorders, including spinal cord injury. The experimental approaches span a number of levels, from mechanical studies of isolated muscle cells to kinematic measurements of natural behavior in quadrupeds.
My laboratory studies a category of lipids, termed sphingolipids, that are important in cell structure, cell-cell communication and signal transduction. This research concerns both complex sphingolipids (sphingomyelins and glycosphingolipids) and the lipid backbones (ceramide, sphingosine, sphingosine 1-phosphate and others) that regulate diverse cell behaviors, including growth, differentiation, autophagy and programmed cell death. The major tool that we use to identify and quantify these compounds is tandem mass spectrometry, which we employ in combination with liquid chromatography for "lipidomic" analysis and in other mass spectrometry platforms (e.g., MALDI) for "tissue imaging" mass spectrometry. To assist interpretation of the mass spectrometry results, and to predict where interesting changes in sphingolipid metabolism might occur, we use tools for visualization of gene expression data in a pathway context (e.g., a "SphingoMAP"). These methods are used to characterize how sphingolipids are made, act, and turned over under both normal conditions and diseases where sphingolipids are involved, such as cancer, and where disruption of these pathways can cause disease, as occurs upon consumption of fumonisins. Since sphingolipids are also components of food, we determine how dietary sphingolipids are digested and taken up, and become part of the body's "sphingolipidome."
Current research is directed at understanding the origin and evolution of RNA assemblies and activities that gave rise to RNA-based genetic and metabolic systems, and the interaction of a bacterial RNA-binding protein Hfq that is crucial for the regulation of gene expression by short regulatory RNAs.
The first research area is examining the assembly and activities of RNA under plausible early earth conditions ( e.g. anoxic environment, freeze-thaw cycles of aqueous solutions). We have shown that Fe2+can replace Mg2+ and enhance ribozyme function under anoxic conditions. Fe2+ was abundant on early earth and may have enhanced RNA activities in an anoxic environments. Freeze-thaw cycles can also promote RNA assembly under conditions where degradation is minimized.
The second area of research is investigating the mechanism of the Hfq protein. Hfq is a bacterial RNA-binding protein that facilitates the hybridization of short non-coding regulatory RNAs (sRNA)to their target regions on specific mRNAs. sRNAs are important elements in the regulation of gene expression for bacteria.Hfq is highly conserved among bacterial phyla and has been shown to be a virulence factor in several bacterial species. The interactions of wild type and mutant Hfq proteins with various RNAs are examined using biochemical/ biophysical methods such as the electrophoresis mobility shift assay, fluorescence spectroscopy, and mass spectrometry.
Microbiology, quorum sensing, regulatory small RNAs, signal transduction, host-pathogen interactions, microbial biofilms.
Our lab studies molecular mechanisms important for microbial interactions. Bacteria are genetically encoded with regulatory networks to integrate external information that tailors gene expression to particular niches. Bacteria use chemical signals to orchestrate behaviors that facilitate both cooperation and conflict with members of the communities they inhabit. We use genetics and genomics, biochemistry, bioinformatics, and ecological approaches with a focus on the waterborne pathogen Vibrio cholerae.
Computational genomics for public health. We are broadly interested in the relationship between genome sequence variation and health outcomes. We study this relationship through two main lines of investigation – human and microbial. Human: we study how genetic ancestry and population structure impact disease prevalence and drug response. Our human genomics research is focused primarily on complex common disease and aims to characterize the genetic architecture of health disparities, in pursuit of their elimination. Microbial: we develop and apply genome-enabled approaches to molecular typing and functional profiling of microbial pathogens that cause infectious disease. The goal of our microbial genomics research is to empower public health agencies to more effectively monitor and counter infectious disease agents.
