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.

 

Phillips Laboratory

research

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.

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.

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.

 

Approaches

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.

Population genomics

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

Functional genomics

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.
Collaborator: Heidi Tissenbaum, Univ. Mass Medical School

Proteomics

We are beginning to use high throughput proteomic approaches to characterize nematode seminal proteins. Collaborators: Willie Swanson and Mike MacCoss, University of Washington

Phenomics

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

Artificial communities

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.

Metagenomics

We are using both traditional and high throughput sequencing approaches to characterize nematode associated bacterial communities.
Collaborator: Brendan Bohannan, University of Oregon

Parallel computing

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