Our lab group is interested in the sensory biology, behavior, neuroethology, and evolution of marine animals. Topics of particular interest include: (1) the navigation of long-distance ocean migrants such as sea turtles, salmon, and spiny lobsters; (2) magnetic field perception, magnetic maps, and use of the Earth’s magnetic field in animal navigation; (3) natal homing and the geomagnetic imprinting hypothesis in sea turtles and salmon; (4) applications of sensory ecology and movement ecology to conservation biology; (5) neurobiology, behavior, and physiology of marine invertebrates; (6) technoethology (the use of novel computer and electronic technology to study behavior). Techniques used range from electron microscopy, immunohistochemistry, and electrophysiology to behavioral studies, oceanographic modeling, and field studies in the ocean. Whenever possible, we favor innovative approaches that cut across traditional academic boundaries and combine elements from disparate fields.

Chromatin and Gene Regulation

Chromosomes are compacted into increasingly complex chromatin structures within eukaryotic nuclei. High-throughput sequence-based assays have been developed to identify regions of nucleosome-depleted open chromatin that mark all types of regulatory elements genome-wide in tissues and cell-types. The computational integration of these data with related gene expression, transcription factor binding, and epigenetic data provide a more complete picture of the complex process of gene transcription and regulation. With these data, we are also investigating the effects of genetic variation on regulation, as can been seen through allelic imbalance in signal from chromatin and transcription factor data, as well as in quantitative trait loci (QTL)-based analyses of these data across individuals. Our computational biology lab both applies established analysis tools to data generated in collaboration with other labs as well as develops new analytical techniques to make novel associations.

Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), primarily consisting of Crohn’s disease and ulcerative colitis, is the result of an inappropriate immune response to the intestinal microbiota in a genetically susceptible individual. We have partnered with Dr. Shehzad Sheikh, MD, PhD (Dept of Medicine, CGIBD) to uncover molecular and microbial characteristics of IBD disease phenotypes. We hypothesize that changes in the chromatin landscape in key intestinal cell types such as macrophages, are influenced by the host genetic background and significantly contribute to aberrant intestinal inflammation. Using both human tissue and mouse models, we seek to identify where chromatin is altered, the impacts on gene expression, the contributions of genetic variation, and the relationship to the microbial community in tissues and cells from affected individuals.

Environmental Toxicogenomics

Exposure to naturally occurring toxicants or by-products of manufacturing process can result in serious health challenges. We hypothesize that toxicant exposure can alter normal cellular function through changes in chromatin architecture and transcriptional profiles in tissues or cells contributing to the onset of medical complications. In a collaboration with Dr. Samir Kelada, PhD (Dept of Genetics), we are investigating the effects of exposure to ozone on the lung inflammatory response in the genetically diverse Collaborative Cross mouse model resource. In particular, we are assaying how ozone-induced chromatin structure and gene expression changes in alveolar macrophages, along with genetic variation, explain variability in ozone response.

How do animals produce and control movement? How does a network of muscles, rigid elements and neurons – components of varying quality and with temporally varying responses – generate robust outputs in the face of uncertain circumstances? For example, the flight of the sphingid moth Manduca sexta is enabled by a complex, hierarchical biological system that involves processes and components at several different levels: the nervous system of the moth activates a suite of 20 flight muscles which actuate mechanical structures (the wings) that do work on the surrounding fluid (air), generating forces to support and propel the moth. These forces lead to changes in position and orientation which are detected by the sensory system and then used, along with underlying feedforward patterns as the basis for future muscle activation patterns, continuing the process and keeping the moth in the air.

Specific Areas of Research:

• Aerodynamics of bird and insect flight
• Neuromuscular and sensory control in animal flight
• Computational approaches to organismal biomechanics

I apply both experimental and computational modeling approaches to these questions, iterating between the two approaches. For example, the figure below shows the wingbeat to wingbeat variation in wing motion during stable hovering flight for both a real moth and a computational model of the moth. In both the model and organism, steady flight behaviour requires continuous slight adjustments.

In addition to investigating the underlying variation of steady locomotion, I also make direct measurements from animals engaged in maneuvering or other unsteady movements. Figure 2 (below) outlines the basis of roll damping in the flapping flight of birds. Surprisingly high roll damping coefficients allow birds to control roll orientation with simple changes in wingbeat amplitude and passively dissipate roll velocity once symmetric flapping resumes.

At a Glance

• Speciation and the evolution of premating isolation
• Sexual selection and the evolution of mate choice
• Learning and cultural evolution
• Evolution of behavior

Synopsis

I am interested in a broad range of topics from evolutionary genetics to behavioral ecology. I explore these topics through the techniques of theoretical biology. My main goal is to use mathematical models to integrate rigorous evolutionary theory with hypotheses explaining behavioral and ecological patterns and phenomena. I am excited to provide integrated approaches to these questions by combining mathematical with experimental, genetic, and comparative techniques through collaborations with students and colleagues.

A large portion of my current work explores mechanisms that drive speciation through the evolution of premating isolation. One of the primary adaptive hypotheses for this evolution is that it occurs through the process of reinforcement, where it is driven by selection against the production of unfit hybrids. I have been exploring reinforcement by trying to pinpoint the forces of selection and genetic associations that cause evolution of alleles for female preferences for conspecific males. A current focus in this area is how speciation processes are affected when mating preferences and/or mating cues are influenced by learning.

An additional area of interest is mate choice, with a particular focus on male mate choice. I have used several different approaches to explore the question of whether male mate choice would be expected to evolve during polygyny. Other projects on mate choice include the effects and evolution of learning on sexual selection.

For more information, please see my lab web page.

Cellular division, wound healing, chemotaxis, and neuronal outgrowth all rely on dynamic shape change and adaptability afforded via an ever-changing cellular scaffold termed the cytoskeleton. We examine two core components of the cytoskeleton: microtubules and actin filaments in concert with the molecules that regulate them and facilitate communication between them. We employ a combined approach of high resolution time-dependent imaging in parallel with atomic resolution protein crystallography and cryo-electron microscopy to understand, at multiple scales, the molecular processes that control cytoskeletal dynamics. Of particular interest are the +TIP protein families that dynamically localize to growing microtubule plus ends where they regulate microtubule dynamics, communicate with the actin cytoskeleton, capture kinetochores, and engage the cell cortex under polarity-based cues. Investigations proceed through three key areas.

1. Structure: Tertiary and quaternary molecular architecture of cytoskeletal regulators attained using x-ray crystallography and cryo-electron microscopy.
2. Cellular and Organismal Imaging: Time-dependent systems analysis via genetic, opto-genetic, and small molecule manipulation.
3. In Vitro Reconstitution: Microscopy-based physico-chemical analysis of cytoskeletal dynamics and convergent biological events (capture, signaling etc.) through titration of core components and regulators.

Interleaving these efforts, we aim to test, correlate, and bridge information gained from the organismal, cellular, sub-cellular and atomic levels. Of particular interest are the aberrant cytoskeletal molecular mechanisms at play in neuronal disorders and cancer biology.

The Vision lab studies genome evolution and the architecture of complex traits, with a (non-exclusive) focus on the flowering plants. Among the questions we ask are:

• What is the genetic basis for ecologically important differences between species, and what evolutionary forces generate that variation?
• What mutational and evolutionary processes are responsible for the structural rearrangement of chromosomes among taxa?
• What effect do genome structural changes have on organismal phenotypes?

To address these questions, we use the tools of both molecular and computational biology, and are actively involved in the development of new computational methods.

The Laederach Lab is interested in better understanding the relationship between RNA structure and folding dynamics. We use a combination of computational and experimental approaches to study the process of RNA folding and assembly. In particular, we develop novel computational approaches to analyze and interpret chemical mapping data. Most recently, we have begun investigating the relationship between disease-associated Single Nucleotide Polymorphisms (SNPs) occurring in Human UTRs and their effect on RNA structure. In particular, we have been investigating regulatory RNA elements called “RiboSNitches,” which like bacterial Riboswitches undergo a large conformational change and regulate translation post-transcriptionally. SNPs in the RiboSNitch cause the conformational change.

My research group investigates the community ecology of infectious disease. We study pathogens infecting wild plants, chiefly grasses. Our main current interest is interactions between fungal pathogens and the broader leaf microbiome.

Adaptations are central to the study of evolution. Thus it is surprising that we know so little about the molecular basis of adaptive evolution. The goal of my research is to identify, clone, and characterize the evolution of genes underlying natural adaptations in order to determine the types of genes involved, how many and what types of genetic changes occurred, and the evolutionary history of these changes. These data will address key questions. For example, do adaptations involve many genetic changes or only a few? How important are regulatory versu! s amino acid changes in adaptation? How often are “new” gene s involved in adaptations? Are most adaptive alleles new mutations or pre-existing alleles segregating at low to moderate frequency within a species? Clearly, a deeper understanding of how genes change during adaptation will give insight into the potential and limits of adaptive evolution.

Spatial patterns of genomic features

I am also using genomic data to address important evolutionary questions. Recently, I used D. melanogaster genome sequence data to estimate genome-wide levels of gene clustering and to contrast the amount of clustering among genes with similar motifs to the levels of clustering in general. All chromosomes, except the fourth, showed substantial levels of gene clusteri! ng. Although not more clustered than the average pair of adjacent genes, genes with the same primary motif occur adjacent to one another more often than expected by chance. These results may mean that these small local groups of genes share regulatory elements and evolutionary histories.

Detecting natural selection in DNA sequence data

Molecular evolutionists have long sought to determine which changes within the protein coding and regulatory regions of a gene were shap! ed by natural selection. If an adaptive substitution has occurred in the recent past, there should be a paucity of DNA polymorphism surrounding the site under selection. Taking advantage of this fact, Andrew Kern and I have developed a permutation approach for detecting selected sites using polarized DNA polymorphism and divergence data. This method is especially useful for detecting the effects of weak selected forces across several loci. We used this approach to analyze a large DNA polymorphism and divergence data set of D. simulans genes. Surprisingly, although replacement fixations do not on average appear to be driven by selection, preferred codons – those codons that use the most abundant tRNA – have on average been fixed by selection. We plan to apply this method to additional data sets and to look at spatial patterns of nucleotide fixation within and around genes. For instance, one could see if there is a bias in the types of polymorphism (sy! nonymous vs. non-synonymous) nearest to a type of fixation. This would give insight into the dynamics of the fixation process and its impacts on adjoining variation.

Selected References   |   Curriculum Vitae  |   Open Positions  |   Currently Seeking Postdocs  |
Dept. Pharmacology Web Page | Potential Students Interested in Joining the Lab

We are interested in cell-to-cell communication. At present, our efforts are focused on signaling that depends on the heterotrimeric G protein complex. Much of our work is devoted to understanding novel mechanisms for activating this pathway therefore we are looking at organisms quite divergent to animal cells where much is already understood about G protein signaling. Using the diversity of life to discover the diversity of cell signaling is a powerful approach.

The JonesLab showed that most eukaryotic cells outside of the animal group have a very different mechanism for activation mechanism. Whereas, the rate-limiting step for G protein activation is nucleotide exchange on the Galpha subunit of the complex, in plant cells and protists, this step is spontaneous. Therefore, the need for a G protein coupled receptor to catalyze this GTP for GDP nucleotide exchange is not needed in plant cells and protists. We showed that the reaction that returns G protein activation (GTP-bound) to the inactive state is the rate-limiting step and is mediated by a receptor like protein that accelerates this “off” reaction. However, this is not the only mechanism to control the pool size of the activated G protein. The JonesLab takes a wide variety of experimental and theoretical approaches to solve central basic problems in cell biology with the intent that our work will translate into improved quality of life, create sustainable agriculture, and make us better stewards of the Earth. Mathematical modelers, biochemists, microscopists, physiologists, geneticists are welcomed to join the JonesLab team. Please see the available positions by clicking the link above.