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Jones, Alan M.

May 4, 2011

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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.

The “G” cycle of animal vs. Arabidopsis
(A) G protein regulation in mammalian cells. In the absence of ligand, G protein forms an inactive heterotrimer with GΒγ dimer (left bottom). Ligand-bound GPCR promotes GDP dissociation and GTP binding on G protein (Top). GTP-bound GΒ dissociates from GΒγ dimer, and both activated GΒ and freely-released GΒγ modulate activity of the effectors (right bottom). GΒ hydrolyses GTP to GDP, and re-binds to GΒγ to return to its inactive state. (B) G protein regulation modeled in Arabidopsis. Arabidopsis G protein (AtGPA1) can spontaneously dissociate GDP and activate itself (left bottom). AtGPA1 does not hydrolyze its GDP rapidly, however AtRGS1, a 7TM-RGS protein, promotes the GTP hydrolysis of AtGPA1 (top). D-glucose or other stimuli functions on AtRGS1 directly or indirectly, and decouples AtGPA1 from AtRGS1 (right bottom). Once released from AtRGS1, AtGPA1 does not hydrolyze its GTP efficiently, maintaining its active state, and modulating the effector activities.

Copenhaver, Gregory P.

May 3, 2011

The genome of any organism is an amazing piece of biology. It is a highly efficient and adaptive information storage, delivery and retrieval device capable of propagating, modifying and repairing itself. As such, understanding how genomes function is central to a broad range of disciplines including genetics, cell biology, biochemistry, developmental biology, and evolution. At the broadest level our lab is interested in understanding how the constituent parts of a genome, chromosomes, function and the dynamic processes that influence them.

To achieve this goal we primarily use the model flowering plant Arabidopsis thaliana. Arabidopsis has a number of characteristics that make it a great organism to study fundamental biological principles. It has a small “completely” sequenced genome with only five chromosomes. It is readily amenable to genetic, cytological and biochemical experimental approaches and it’s near world-wide distribution makes the use of natural variation a powerful tool. Also, here in the biology department at UNC-CH there is a particular emphasis on the use of Arabidopsis as a model system.

My lab is primarily interested in understanding how meiotic recombination is regulated at the genomic level in higher eukaryotes. While significant progress has been made in understanding many of the molecular components of the recombination process in lower eukaryotes like the yeast S. cerevisiae, far less is known about similar functions in complex multi-cellular organisms. Because of the complexity of higher eukaryotic genomes, the high level of gene duplication and divergence, the presence of DNA modification and the organization of multiple chromosomal domains into heterochromatin the molecules that govern meiotic recombination in these organisms are likely to be novel and of significant biological interest. Additionally, their identification may have practical benefits, contributing to our understanding of human disease genes and providing useful tools for agricultural bioengineering.

A second research area in the lab is investigating the role of centromere DNA in chromosome biology. Centromeres are the chromosomal domains that direct segregation during cell division by mediating a number of critical functions including: attachment of the chromosomes to the spindle microtubules, nucleation of kinetochore proteins, and maintenance of sister chromatid cohesion. Arabidopsis centromeres are some of the best characterized among higher eukaryotes. Currently the efforts in the lab are focused on obtaining a complete definition of the DNA within the genetically defined centromeres of Arabidopsis.

Grant, Sarah R.

May 3, 2011

Interaction of plants and microbes. I no longer supervise students or postdoctoral fellows. I remain a member of Jeff Dangl’s research group. The Dangl group investigates the plant immune system and its influence on the communities of environmental microbes associated with plants.

See publications here.

Crews, Stephen

April 21, 2011

At a Glance

  • Formation and differentiation of Drosophila neurons and glia
  • Regulation of nervous system transcription

Our laboratory is concerned with the molecular mechanisms that govern the development of the Drosophila central nervous system, including: (1) how nervous system precursor cells are generated, and (2) how neurons and glia acquire their differentiated properties. The primary focus of the lab is using genomic technologies to study the regulation of transcription during neuronal and glial development.

Ahmed, Shawn

April 12, 2011

Our research group has interests in telomere biology and germline immortality. We are studying these problems using the nematode Caenorabditis elegans, a multicellular eukaryote with excellent genetics, which can be combined with biochemical and cell biology approaches.

How does the germline achieve immortality?

The germline is an immortal cell lineage that is passed from one generation to the next, indefinitely. In order to determine how germ cells achieve immortality, we have identified C. elegans mutants with Mortal Germlines: mutants that reproduce normally for several generations, but eventually became sterile (Figure 1). Gametes of these mutants transmit forms of stress that can accumulate over the generations to levels that cause strong effects on germ cell development (sterility or reproductive arrest). Stress transmitted by mortal germline mutants could also affect somatic development. One pathway that promotes germ cell immortality is the Piwi/piRNA genome silencing pathway. Deficiency for this pathway allows for growth for many generations but then results in an adult reproductive arrest phenotype that resembles a response to acute starvation. Furthermore, deficiency for the daf-2 insulin/IGF1 receptor, which results in stress resistance and adult longevity, can suppress the sterility of Piwi mutants. This creates an interesting link between germ cell immortality and somatic longevity whose basis we seek to understand.

Figure 1. mortal germline mutants eventually become sterile after several generations.

Given that the soma is only needed for a single generation, evolutionary theory posits that somatic cells may be deficient for pathways that ensure germ cell immortality. Substantial evidence from vertebrates indicates that this is likely to be the case. We utilize genetic, cell biology and biochemical approaches to study pathways that enable germ cells to achieve proliferative immortality in C. elegans. This work could shed light on epigenetic forms of macromolecular stress that can be transmitted by gametes and could be generally relevant to heredity and possibly to human disease.

Analysis of Telomere Biology

A second pathway that promotes germ cell immortality is telomerase, which is a ribonucleoprotein that adds repeats to chromosome termini. The ends of linear chromosomes, telomeres, are usually composed of simple repetitive sequences whose length is maintained by telomerase. Humans deficient for telomerase suffer from the lethal hereditary disorders Aplastic Anemia, Dyskeritosis Congenita and Pulmonary Fibrosis. C. elegans is the most highly evolved multicellular eukaryote in which an unbiased genetic approach can be used to study the problem of telomere replication. A fraction of the mortal germline mutants described above are completely defective for telomerase activity in vivo (Figure 2). Studies of these genes may help to elucidate the mechanism by which telomerase functions at chromosome termini and may provide significant insight into telomerase-related diseases. We also study proteins that bind to telomeres, some of which form nuclear foci that are dynamic during development.

Telomerase is deficient in most human somatic cells, and telomere erosion in this context may contribute to genome instability that fuels the development of many forms of cancer. C. elegans has holocentric chromosomes, so fused chromosomes that occur when telomerase is deficient can be genetically isolated and mapped. These stable end-to-end chromosome fusions allow us to address the mechanism by which dysfunctional telomeres are repaired with unparalleled clarity, and may provide insight into how large-scale DNA rearrangements occur during tumorigenesis.

Figure 2. Teomere replication defects such as (a) telomere shortening and (b) end-to-end chromosome fusions are observed in a subset of mortal germline mutants, suggesting that teomerase does not function properly in these mutants.

Burch, Christina

April 8, 2011

I have taken an experimental approach to the study of evolution because it allows me to address questions from many areas of evolutionary biology. Evolution experiments using microorganisms have been able to address widely ranging topics from kin selection and the evolution of virulence to the evolution of mutation rates, and the evolution of habitat (or host) specialization.

Although I am interested in all aspects of evolutionary biology, and students and postdocs in my lab are encouraged to develop independent projects that follow their own interests, the primary focus of my work has been to investigate the genetics of adaptation. I am using laboratory evolution experiments of bacteriophage (bacterial viruses) to address the following questions:

  • Does adaptation occur by large or small steps?
  • Are certain genotypes better able to adapt than others?
  • Can we identify factors that shape the nature of interactions between mutations?

Bacteriophage serve as particularly suitable systems for addressing the genetics of adaptation because they offer the opportunity to observe events on an evolutionary timescale within weeks or even days. For example, we can watch evolution of the bacteriophage phi-6 in action simply by monitoring increases in plaque size . As beneficial mutations appear and become common in adapting populations, fitness improves and plaque size increases.