We believe that all research must be conducted within a strong conceptual framework. We therefore seek a balance of empirical and theoretical approaches to solving fundamental questions in biology, whether they be in evolution, molecular genetics, or ecology.
Research in the Phillips lab spans a wide range of biological questions, from molecular genetics to evolutionary ecology. The central thread of our work is the use of genetic, experimental and theoretical approaches to address fundamental questions in evolutionary biology. We primarily use the model nematode Caenorhabditis elegans and its relatives (particularly C. remanei) for our empirical work.
Deterministic and stochastic effects of diet on demography
Systems genetics of natural variation in stress response pathways
Genetic variation underlying the response to longevity interventions
META: Microbial Ecology and Theory of Animals
NIH Center of Excellence in Systems Biology
NIH P50 GM098911
The current core research areas in the lab are:Evolutionary genetics of aging and stress response
Many of the key insights into the genetic basis of aging have been made in C. elegans. We are capitalizing on this knowledge to understand the genetics of natural variation in aging and the response to a wide variety of environmental stressors (e.g., heat, oxidation, pathogens) in C. remanei. We are conducting large scale experiments selecting on the response to both chronic and acute stress. We are analyzing genetic variation both at the level of the physiological response and in the underlying signal transduction and response networks.Diet, development and individuality
Caenorhabditis nematdoes make their living by eating bacteria and other microorganisms. Variation in diet has been shown to be a major determinant of live history changes within these worms, with starvation inducing diapause or resting stage at several distinct phases of development and dietary restriction leading to life extension. We are using the precision that is possible using microfluidics to study the effects of dietary variation within and between bacterial species on worm developmental and reproductive patterns, including dissecting the genetic pathways responsible for transducing these signals and investigating the transgenerational effects of dietary changes.Compound/drug interventions that increase lifespan
Researchers have begun to identify chemical compounds that can extend life in model organisms. We are part of a large NIH sponsored program with Gordon Lithgow (Buck Institute of Aging) and Monica Driscoll (Rutgers University) investigating the influence of genetic variation within and between species on the efficacy and robustness of these compounds. This is also one of the largest studies on the reproducibility of aging results ever conducted.Evolution of sex, outcrossing and sexual conflict
Nematodes show unusual variation in mating systems. C. elegans is androdeocious (males and hermaphrodites), while most other members of the genus are dioecious/gonochoristic (males and females). We capitalize on detailed knowledge of the C. elegans sex determination system and use experimental evolution to examine the role of males and outcrossing in facilitating evolutionary change. We also use molecular quantitative genetics to investigate what makes "good" males and females, and what allows males to be maintained at high frequencies in some populations but not in others. The high frequency of males in dioecious species like C. remanei provides a strong opportunity for sexual selection and sexual conflict, which we are investigating using genetic, genomic, proteomic, as well as more traditional behavioral, approaches.Evolution of gene interactions and genetic networks
Standard evolutionary theory has yet to fully come to grips with the massively interactive structure of gene regulatory systems. We are looking at the evolution of genetic networks using both empirical and experimental approaches. For example, we have been looking at the molecular evolution of chemosensory, insulin signaling and micro RNA regulation pathways in nematodes. We are also doing theoretical work on the evolution of network structure, including modeling the yeast synthetic lethal network.
Molecular quantitative genetics of behavior
We have used genetic mapping approaches to dissect complex epistatic interactions that underlie natural variation in both chemosensory and thermosensory behavior, with more recent focus on the latter. As ectotherms, temperature has a dramatic effect on these nematodes, and so we have been examining temperature-fitness relationships from the standpoint of physiological ecology as well.
Ecological genetics of bacteria-nematode interactions
One of the weaknesses of the nematode system is that the ecology is poor. In collaboration with Bohannan lab (Univ. Oregon), we have been characterizing natural bacterial communities living in association with wild-caught nematodes and have begun characterizing the fitness effects of these bacteria, examining nematode food preference, etc. We have also constructed artificial dirt microcosms for conducting population cage experiments.
Evolutionary ecology of frog development
Although we do not currently perform any research on amphibians in the lab, we are involved in a long term collaboration with Robert Kaplan (Reed College) that examines the influence of environmental variation and local adaptation on the development of larval frogs. Although there are logistical barriers, we would eventually like to start exploring similar questions directly within our lab.
In addition to standard techniques such as genetic crosses, statistical genetics, DNA sequencing, cloning, molecular population genetics, and computer simulations, we have been active in developing novel approaches to addressing these research questions.
We have helped to pioneer the use of C. elegans and its relatives as model systems for the use of experimental evolution in asking evolutionary questions that range from the evolution of sex and outcrossing to the changes in phenotypic plasticity and transgeneration inheritence for stress response. Nearly every project that goes on in the lab includes some component of experimental evolution.
Collaborator: Henrique Teotonio, École Normale Supérieure, Paris
We use whole genome resequencing and high density maker analysis (RAD) to characterize to analyze nematode molecular evolution. We are in the process of refining the genome sequence and genetic map of C. remanei.
Collaborators: Bill Cresko, University of Oregon; Asher Cutter, University of Toronto
We use a variety of protein-associated DNA approaches (e.g., ChIP-seq) and whole genome transcriptional analysis to characterize complex regulatory relationships among genes and other regulatory elements.
We are beginning to use high throughput proteomic approaches to characterize nematode seminal proteins. Collaborators: Willie Swanson and Mike MacCoss, University of Washington
Now that we can have total genomic knowledge regarding any individual, on of the great challenges in evolutionary biology is obtaining large amount of high quality phenotypic data on thousands of individuals. Nematodes are very small (~1 mm) and easily manipulated in liquid, making them ideal candidates for microfluidic approaches, which involve engineering liquid control circuits much like one generates computer circuits. We have developed microfluidic chambers for assessing thermal preference behavior and hope to develop high throughput phenotyping approaches in the future.
Collaborator: Shawn Lockery, University of Oregon
Most research in this group of nematodes has been carried out in the lab on Petri dishes in which the worms are literally swimming in their food. We have recently perfected an approach to raising the worms in “artificial dirt” communities that allows both long term maintenance at large population sizes (i.e., population cages) and more complex bacterial ecosystems.
We are using both traditional and high throughput sequencing approaches to characterize nematode associated bacterial communities.
Collaborator: Brendan Bohannan, University of Oregon
Investigating the population genetics of large (e.g., empirically motivated) genetic networks is computationally intensive. We are developing highly parallelized approaches to addressing these questions using the new multi-million dollar computer cluster at the University of Oregon (ACISS).
Collaborator: John Conery, University of Oregon