David Bird
Bio
David Bird received a Ph.D in Biochemistry from the University of Adelaide, Australia in 1984, followed by three years researching C. elegans developmental genetics with Dr Don Riddle at the University of Missouri-Columbia. Dr Bird joined the faculty of the University of California-Riverside, and in 1995 moved to NC State University to join the faculty in Plant Pathology. Dr Bird has served on numerous university and professional panels and committees, including having served as Chair of the University Research Committee, as Editor-in-Chief of the Journal of Nematology, and as Director of the NCSU Bioinformatics Research Center, and as Director of the university’s Genomic Sciences Graduate Program. In 2012, Dr. Bird was named William Neal Reynolds Distinguished Professor.
Research:
Dr. Bird’s research interests include: nematode biology and development; genome organization and evolution; structure-function relationships; host-parasite interactions; evolution of parasitism.
The primary focus of his research group is to understand the mechanisms underlying parasitic interactions between nematodes and plants. David was a pioneer in framing the key questions in the context of nematode and host development. Together with collaborators world-wide, his group has been instrumental in establishing the root-knot nematode, Meloidogyne hapla, as the preeminent genetic system to model less-tractable nematode-host interactions, and as a platform for comparative genomics (www.hapla.org). His current program also emphasizes vaccine development for malaria-like diseases of cats and dogs.
Teaching:
Dr Bird teaches in two classes: PP501, and PP610/810
Publications
- Toward genetic modification of plant-parasitic nematodes: delivery of macromolecules to adults and expression of exogenous mRNA in second stage juveniles , G3-GENES GENOMES GENETICS (2021)
- A Single, Shared Triploidy in Three Species of Parasitic Nematodes , G3-GENES GENOMES GENETICS (2020)
- Bacterial Community Structure Dynamics in Meloidogyne incognita-Infected Roots and Its Role in Worm-Microbiome Interactions , MSPHERE (2020)
- Infection by cyst nematodes induces rapid remodelling of developing xylem vessels in wheat roots , SCIENTIFIC REPORTS (2020)
- Identification of Cytauxzoon felis antigens via protein microarray and assessment of expression library immunization against cytauxzoonosis , CLINICAL PROTEOMICS (2018)
- Disparate gain and loss of parasitic abilities among nematode lineages , PLOS ONE (2017)
- Networks Underpinning Symbiosis Revealed Through Cross-Species eQTL Mapping , Genetics (2017)
- Genetic Drift, Not Life History or RNAi, Determine Long-Term Evolution of Transposable Elements , GENOME BIOLOGY AND EVOLUTION (2016)
- Mitochondrial Genome Sequences and Structures Aid in the Resolution of Piroplasmida phylogeny , PLOS ONE (2016)
- PCR amplification of a multi-copy mitochondrial gene (cox3) improves detection of Cytauxzoon felis infection as compared to a ribosomal gene (18S) , VETERINARY PARASITOLOGY (2016)
Grants
Primary focus of this project is the cure and prevention of cytauxzoonosis.
Primary focus of this project is to discover and evaluate Cytauxzoon felis genes and proteins for the purpose of diagnostic assays, vaccine antigens and novel drug targets.
Cytauxzoonosis is a life-threatening disease of domestic cats caused by the tick-transmitted apicomplexan protozoan parasite Cytauxzoon felis that is closely related to Theileria, Babesia and Plasmodium (the causative agent of malaria). Without treatment 97% cats with cytauxzoonosis die. Even with the best available treatments, morbidity is extreme and mortality rates approach 40%. Regardless of outcome, treatment can cost thousands of dollars per case. Since its discovery in the 1970s, the geographic distribution of this parasite has grown rapidly and cytauxzoonosis is now diagnosed in 35% of the states in the continental USA. The distribution of C. felis is likely to expand further and threaten even more cats as the primary vector, the lone star tick, extends its distribution. The high mortality and growing epidemic point to vaccination as the only practical control strategy. Unfortunately no vaccine against C. felis exists. In fact, prior to our work, no C. felis antigens had ever been characterized. Nonetheless, evidence does suggest that cats surviving infection develop protective immunity. Two major barriers to antigen discovery and subsequent vaccine development include the inability to culture C. felis in vitro and a lack of funding for feline specific diseases. Federal agencies focused on human and food animal health stopped funding C. felis research once it was recognized in the early 1980s that cytauxzoonosis was limited to domestic and wild felids. In order to overcome the limitations posed by an inability to culture the parasite in vitro, we have recently sequenced, assembled and annotated the entire 9.1 Mbp C. felis genome. This has enabled us to identify ??A!??a?? 4,300 C. felis protein-coding genes, each of which represents a possible protective antigen. Our challenge now is to identify and prioritize which of these genes are the best vaccine candidates. We hypothesize that high throughput immunoscreening using C. felis protein microarrays will result in the rapid identification and prioritization of a large number of potentially protective C. felis antigens representing excellent targets for a C. felis vaccine.
In this proposal, we will examine the relationship between a plant (Medicago truncatula) and a root knot nematode pathogen that infects that plant's roots. Our goal is to observe how the genetic code of the pathogen influences the biological responses of the plant, specifically at a gene transcription level. To address this question, we implement a technique known as expression quantitative trait locus (eQTL) mapping, which combines gene expression studies together with genetic linkage mapping. This technique is designed to investigate connections between DNA sequence changes and gene expression levels, in a way that compares each region of the genome to every expressed gene. We are transforming this approach to allow a cross-species investigation, in which each each region of the pathogen genome is compared with each expressed plant gene. We follow up on our results from this analysis with gene network identification, in order to characterize more complex cross-talk between species. The results of this study will be fundamental to furthering our understanding of not just plant defenses and susceptibility, but also the myriad of ways in which the pathogen influences the physiology and development of its plant host.
Agricultural productivity is a foundational component of the US economy. Advances in traditional animal breeding, nutrition, and immunology have made us a worldwide leader in animal agriculture; however with the threats of global warming, globalization, and competition from countries such as China and Brazil it is imperative that we aggressively develop new technologies if we are to ensure our position of leadership. With the completion of several food-animal genomes, attention must now be placed on how to translate genomic information into practical applications. To do this, a new generation of scientists must be trained. Herein, we propose an integrated program of graduate training, research, and industry outreach designed to meet the national need for animal/poultry scientists trained in the emerging functional genomics discipline. The objectives are to: 1) attract three exceptional pre-doctoral students in the targeted area of Agricultural Genomics and Bioinformatics, emphasizing Functional Genomics of animal agriculture; 2) provide students with inter-disciplinary training, merging Functional Genomics, Bioinformatics, and Animal/Poultry Sciences; 3) provide students with significant training in online learning. We will meet these objectives by taking advantage of existing curricula and resources at NCSU. The National Needs Fellows will be recruited into the Functional Genomics graduate program, with a concerted effort to recruit students from under-represented groups by partnering with other UNC system universities. The graduates of this program will be leaders in the emerging online learning environment, developing rational pedagogies and technologies for instructional and outreach activities. These Fellows will enhance the competitiveness and sustainability of US farm communities and strengthen our capacity for international trade.
Significant agricultural damage is caused by obligate plant parasitic nematodes, particularly root-knot nematodes (RKN: Meloidogyne spp). RKN infection is characterized by gross yield loss and macroscopic root-galls, at the heart of which are specialized and dedicated feeding sites. Feeding sites form as a direct consequence of an intimate host-parasite relationship, and corruption of normal plant development. The goal of this project is to better understand the molecular mechanisms by which these feeding sites are formed. In particular, I will explore the role(s) of RKN-encoded peptide signaling molecules. Using a computational approach I have identified genes encoding families of plant peptide hormone analogues in the RKN genome including nine C-terminally encoded peptides (CEP), eight CLAVATA-like elements (CLE) and a rapid alkylinization factor (RALF). My project goals are: [1] Comprehensively characterizing transcriptionally active RKN genes with sequence similarity to plant genes encoding peptide hormones; [2] Developing bioassays to functionally characterize RKN-encoded, plant peptide-hormone mimics; [3] Defining the roles nematode peptide hormones play in plant parasitism by RKN; [4] Elucidating the molecular mechanism(s) by which nematode peptides interact with host tissue. My preliminary data inform a new model for RKN parasitism and suggest new targets for transgenic or chemical control. Defining multiple novel targets and their roles in nematode parasitism directly addresses the first Program Area Priority; to ?keep American agriculture competitive while ending world hunger.? I have established an advisory committee with complementary expertise to mentor my profession development and project goals, in concert with the unique enrichment opportunities provided by NCSU.
Intimate associations between microbes and eukaryotes are widespread in nature, occurring in every type of ecological niche (Margulis, 1998). The spectrum of such interactions ranges from highly integrated obligatory symbioses to ?loose? associations (Margulis, 1998; Bordenstein, 2003). Symbionts have adapted to their hosts with astounding sophistication, being able, in many cases, to control their reproduction, behavior and overall physiology (Cheng, 1970; Douglas, 1994; Ishikawa, 2003). Key questions in the study of symbiosis include how microbes move between host species, how host and microbe adapt to each other physiologically and genetically, and what evolutionary consequences result from microbial-host associations. One of the most common eukaryote-prokaryote interactions is that between nematodes and bacteria. The range of associations between nematodes and bacteria is incredibly broad, ranging from fortuitous to obligate and from beneficial to pathogenic. Moreover, this extensive spectrum of symbioses occurs in all possible habitats. TAt present, numerous researchers worldwide are studying associations between these two groups of organisms, but these scientists occupy many different disciplines, and often do not interact. The scope of such research is mostly dictated by nematode trophic groups. For example, because of their importance as human parasites, the association between filarid nematodes and Wolbachia has received significant attention. Similarly, because of their utility for insect control, interactions between insect-pathogenic nematodes and symbiotic bacteria are a major research topic. Researchers interested in biocontrol of plant-parasitic nematodes are interested in bacteria that parasitize the nematodes directly and the discovery of horizontal transfer of genes from rhizobacteria to nematodes has drawn interest from biologists studying genome evolution. Not surprisingly, these researchers come from diverse backgrounds in medicine and veterinary science, entomology, plant biology, genetics etc., yet to date no common coherent ground exists connecting the science being done in this discipline, despite the fact that advances in each will undoubtedly inform the others. Furthermore, a comparative approach has the power to reveal common underlying themes of nematode-bacterium associations as well as fundamental aspects of symbiosis.T We propose to promote the intellectual discourse among scientists studying bacteria-nematode associations by organizing a Research Coordination Network on ?Nematode-Bacteria Symbioses?. A diverse group of scientists (including women and underrepresented minorities) will create the research and education network, to execute three goals: 1) Foster interdisciplinary collaborations between scientists; 2) Encourage scientists engaged in basic and applied research to explore how cross-talk and networking can enhance and advance science in this field: 3) Develop and distribute educational materials to nematologists, microbiologists and educators to consider and promote the study of nematode-bacteria symbioses as biological model systems in science and education. Participants will meet at least once a year in each of the five years of funding to discuss and exchange ideas on research priorities, analytical methods and other matters appropriate to a theme to be selected for each year of this network effort. During these meetings, cooperation and collaboration among scientists in related and/or different fields in the study of nematode-bacteria interactions will be fostered. In addition to this, focus will be placed in the creation and dissemination of educational initiatives at different levels including elementary, high school and college levels. Efforts will be placed to include postdoctoral associates, graduate students, and undergraduates into this enterprise, along with foreign colleagues. Rapid communication will be accomplished by electronic means and through public access to a web site established for the RCN activity.
Dog patients have been proposed to be an attractive animal model to study the etiology and clinical therapy of Non Hodgkins Lymphoma, but the value of such a model depends on a reliable classification that can distinguish canine DLBCL into subgroups that correspond to humans. In our research, we will perform a comparative molecular analysis of human and canine DLBCL with respect to gene expression profiling, immunoglobulin gene, mutations in Prdm1, and constitutive NF-kB signaling. We aim to develop a reliable classification to distinguish the similar subtypes in canine DLBCL and elucidate the advantages of canines as an excellent disease model.
Plant parasitic nematodes cause more than $100 billion in annual crop loss worldwide; root-knot nematode (RKN: Meloidogyne spp.) is especially devastating. This proposal will employ genomic/proteomic tools to address the earliest events in the interaction of Meloidogyne hapla with its host, including perception of chemical signals from the plant. We postulate that host recognition will induce substantial gene expression and post-transcriptional changes in the nematode that make it particularly vulnerable to intervention for control. We will use multi-dimensional liquid chromatography and tandem mass spectrometry (MS/MS) to obtain the basal proteome of pre-penetration M. hapla. Proteins will be identified from a database we will build from the 20,908 proteins deduced from the ~62,000 RKN ESTs we previously obtained, as well as from 10,000 M. hapla full-length cDNAs we will generate in this project. Using stable isotopic labeling, we will identify changes in the proteome associated with perception of the plant host by MS/MS in conjunction with bio-assays to study perception of the plant host by M. hapla. We will design a unigene set including >8,000 M. hapla sequences and construct a cDNA-based microarray to interrogate the M. hapla transcriptome during host perception. Candidate genes will be subjected to RNAi-mediated gene ?knock-down? to examine their function during host recognition. The approach we propose addresses the priority mission area of agricultural genomics. Further, our large-scale and high-throughput approaches will develop resources and databases to address broad issues in future nematode control and are thus directly pertinent to future food production and enhancement of environmental quality.
Plants establish symbioses with diverse soil microbes, ranging from beneficial mutualists, such as mycorrhizal fungi and nitrogen-fixing rhizobacteria, to devastating parasites such as nematodes. Plant parasitic nematodes cause more than $100 billion in annual crop loss worldwide; root-knot nematode (RKN: Meloidogyne spp.) has the most economic impact. From prior research, we have found that the initial response of plants to RKN is very similar to the response of legumes to beneficial symbionts, and genetic analysis confirms that these responses indeed are germane to establishment of the parasitic interaction. Preliminary evidence points to the existence of a signal (Nematode Factor: NemF) produced by RKN, which has functional similarity to rhizobial Nod factor. Our hypothesis is that during their evolutionary history, RKN have become adapted to exploit the plant machinery used by rhizobia and mycorrhiza to establish symbioses as a means for the nematodes to enhance their parasitic ability. This project will use confocal, DIC and video fluorescence microscopy to study the dynamics of RKN infection of plants to subcellular resolution. We will exploit existing legume mutants to dissect the RKN response pathway, and we will perform functional analysis of the orthologous genes in tomato using virus-induced gene silencing (VIGS). The VIGS experiments will directly test the role of particular plant genes and pathways in the parasitic interaction. Finally, we will establish a bioassay for NemF, and we will use liquid- and solid-phase extraction mass spectrometry to fractionate and characterize NemF. This project directly addresses all three of the FY 2006 Priorities for Research of the Suborganismal Biology and Genomics of Arthropods and Nematodes Program and the CSREES goal to Enhance protection and safety of the Nation?s agriculture and food supply.