Our Science
"The CRG undertakes genomically-informed research on issues of significance related to mammalian reproduction, health and disease."
The strength of this approach derives from the use of an ever-increasing body of genomic resources, in a comparative, evolutionary framework, to derive new knowledge of the key similarities and differences among our study systems, whether these be species, populations or individuals. This approach provides a framework from which we can rapidly identify new genetic candidates for simple and complex traits, better understand biochemical and developmental pathways, develop new biological and biomedical models, and ultimately gain technological improvements to animal production, animal and human health (Figure 1).
Figure 1. An integrated, genomically-informed, approach for research at the CRG
Research Programmes and Projects
Programme 1. Investigating fertilisation and early events in embryogenesis
Programme 2. Gamete Biology
Programme 3. Vertebrate sex determination and sex allocation
Programme 4. Comparative and evolutionary genomics
Programme 5. Reproductive and genomic tools for conservation and biocontrol
Programme 6. Genomic tools for non-classical species
Programme 7. Livestock species as models for human disease
Programme 1. Investigating fertilisation and early events in embryogenesis
1) Male-female interactions and cryptic female choice
There is increasing evidence that the fusion of gametes in many species is non-random, with a variety of receptors and their ligands now identified on both sperm and egg. Coupled with this is a considerable body of evidence that suggests females may control fertilisation after mating – a process called cryptic female choice (CFC). Recently we demonstrated in salmon that ovarian fluid differentially alters male sperm function in a female-dependent fashion, suggesting that females exert cryptic control of male reproductive success. The rationale for this CFC is unknown, but ovarian-fluid-mediated sperm selection may promote favoured genetic combinations that enhance offspring fitness. Using state-of-the-art sperm analyses, competitive fertilisations, and parentage assignment we will determine if this differential sperm function affects male fertilisation success and if so whether there is a genetic basis for the observed CFC. We anticipate that this work will enhance greatly our knowledge of CFC, a phenomenon likely to be widespread in Nature but poorly understood. Understanding the mechanisms and rationale for CFC may help explain the significant differences reported between expected and realised male reproductive success across an ever increasing list of taxa, including species significant to conservation, agriculture and aquaculture. For medical science, improved knowledge of CFC may herald better outcomes for the ~28% of infertile couples suffering from “unexplained infertility”, a component of which may be due to hereto-unidentified CFC. There are further prospects for us to explore CFC beyond salmon and we welcome discussion with potential students, postdoctoral fellows and collaborators in this area. (Gemmell)
2) Epigenetic reprogramming by sperm-derived factors
When sperm meets egg a cascade of events takes place, including the unpackaging of the male pronucleus, the reprogramming of male and female pronuclei, and ultimately their fusion, upon which the zygote is formed and subsequently propelled through the various phases of development. These events are poorly understood at a molecular genetic level but work using somatic cell nuclear transfer suggest that what comes in with the sperm, or is initiated within the egg as a consequence of fertilisation is an important determinant of embryo survival and growth. Using next generation sequencing of transcriptomes from sperm, eggs and early embryos of cattle and mouse models we seek to unravel much of the mystery surrounding these events. We welcome expressions of interest from potential students, postdoctoral fellows and collaborators in this area (Oback, Gemmell)
3) Placentation and early embryo survival
The placenta is a crucial organ, facilitating nutrient and gas exchange between the mother and foetus, altering maternal physiological conditions to sustain pregnancy, while also protecting the foetus from the maternal immune system. Abnormalities in placental development are associated with early pregnancy failures in humans and animals. There is likely a genetic basis for many of these failures, but few candidate genes have thus far been identified. Knowledge of the genes involved in placenta formation and function would provide useful targets for further study of the genetic basis of variability in placentation and the growth and survival of the foetus. Using a comparative genomic framework and new genomic resources from the platypus, opossum, wallaby and 17 placental mammals we seek to rapidly identify key genes involved in placental development and function – the recently published bovine genome estimates 1217 genes occur only in placental mammals, and this gene set constitutes the starting point for our programme. We welcome expressions of interest from potential students, postdoctoral fellows and collaborators in this area (Gemmell, Demmers, Maqbool)
Programme 2. Gamete Biology
4) Oogenesis, follicular development and ovulation
This has been a flagship area of research for AgResearch for many years, with great in roads made to improve prolificacy of livestock species, including the discovery of several mutations in genes involved in ovulation that lead to heightened ovulation rates. There are further prospects for us to explore prolificacy in livestock and other systems and we welcome discussion with potential students, postdoctoral fellows and collaborators in this area. (Juengel)
5) Sperm formation and function
Males seldom command a premium in agricultural systems, with one or two high performance males generally all that is desired for breeding purposes. However, there is significant interest in sperm formation and function in humans, where male factor infertility accounts for about 1/3 of infertility, a condition that now affects 15% of couples in the western world. While as yet in its infancy there are good prospects to utilise livestock species to better understand the factors that influence male fertility. In addition, aspects of work on male infertility could lead to new opportunities for male contraceptives and approaches to biological control. A well established research programme on the importance of the mitochondrial genome on sperm function is already underway in the Gemmell lab, where we have been using salmonid systems to explore the role of this molecule on sperm function and male reproductive success. Other project ideas include: what’s in a sperm, the function of the epidymidis in sperm maturation and the role of accessory gland fluids on sperm function. We welcome discussion with potential students, postdoctoral fellows and collaborators in this area. (Gemmell)
Programme 3. Vertebrate sex determination and sex allocation
6) Sex determination in fish
Vertebrate sex determination runs a gamut of forms spanning environmental through to chromosomal sex determination. Among the vertebrates fish display the greatest diversity of sex determination systems and perhaps as a consequence of this diversity the molecular pathways leading to sex determination in fish are the least well understood. Fish are the most basal and the largest of the vertebrate groups, thus their absence from a comparative framework of vertebrate sex determination makes the determination of the ancestral state and the origins of the myriad sex determination systems observed in modern vertebrates challenging. We are addressing this major gap in knowledge using zebrafish and salmon as models to explore the genetic basis of sex determination and differentiation in teleost fish. Using a novel combination of experimentally induced sex reversal, transcriptomic screens, and bioinformatic comparisons we will rapidly identify the common and unique elements of sex determination in fish greatly increasing our knowledge of sex determination in the largest, most diverse, and most basal of vertebrates. We welcome discussion with potential students, postdoctoral fellows and collaborators in this area. (Gemmell)
7) Sex allocation
There is increasing awareness that the sex ratios at birth in many species are highly skewed. To explain this observation Trivers and Willard hypothesised more than two decades ago that there might be a strong environmental effect operating on females to produce offspring of a particular sex. In particular they put forward the idea that female’s in good condition might invest more energy in sons, providing greater benefit to the individual in terms of their lifetime reproductive fitness. While this notion is now well established, and there is good experimental evidence in a number of systems, particularly birds and mammals, the mechanisms remain unknown. Livestock species, such as sheep, cattle and deer, provide tractable systems in which to experimentally test sex allocation theory, and when coupled with the breeding records, reproductive and genomic data, held by AgResearch we have in place a system that could be utilised to identify the proximal and ultimate mechanisms through which sex allocation operates. At present this project is no more than a concept, but we welcome discussion with potential students, postdoctoral fellows and collaborators in this area. (Gemmell)
Programme 4. Comparative and evolutionary genomics
8) Molecular marker evolution
A variety of molecular markers are now applied widely to investigate population and evolutionary processes in numerous species, including modern humans. Despite their wide use there is a paucity of information on evolutionary properties of the various molecular markers. Such knowledge is vital if we are to ensure that evolutionary interpretations based on these molecular data are accurate. The Gemmell group has several projects underway to use recent developments in molecular biology, bioinformatics and genomic sciences to investigate microsatellite and mtDNA evolution. Currently, we are investigating the role of recombination in microsatellite evolution in a yeast model that various does and does not engage in sex (Gemmell), and utilising new genomic data and technologies to investigate the evolution of copy number variants (CNVs) (McEwan), using next generation sequencing to test for direct evidence of mtDNA recombination (Gemmell and Phua). We welcome enquires from potential students, postdoctoral fellows and collaborators in this area.
9) Genomic scans for identification of candidate genes
The completion of the genome sequences for a large number of species, together with fast, cost-effective systems to screen diversity within and among species at scales never before available, heralds a new era in biology. We are exploiting this new information using cross-genomic comparisons to identify conserved, and divergent genomic components. These components represent, respectively, the core gene set shared among a group of organisms, whether they be individuals, breeds, populations or species, while those that differ encompass those genes responsible for the phenotypic and behavioural differences among the groups being studied. For example, cattle have about 1000 genes not found in human, a scale of difference similar to that previously observed in rat and dog. Each has interest to us as we seek to understand the genetic basis of specific traits of interest, whether they be attempts to identify genes involved with particular evolutionary transitions in reproduction e.g. placental genes (project 3) or the search for genes associated with parasite resistance, meat traits, fat colour etc. in sheep that are already underway using the Ovine 50K SNP chip. There are numerous opportunities in this space as we sift through the large body of data to identify the gene/s associated with a various phenotypic and behavioural traits associated with e.g. different sheep breeds and we welcome discussion with potential students, postdoctoral fellows and collaborators in this area. (McEwan, Johnston, Fisher and Gemmell).
10) Genome evolution
We now have opportunities that extend beyond simple candidate gene identification. We have the data, resources and tools to cut to the heart of issues relating to the importance of genomic composition, genome arrangement, genomic packaging etc. on genomic regulation, and we can also examine the differential effects of evolutionary forces on the various components of genomes. The completion of genomic sequences for many species, and the focus on sequencing multiple genomes for some e.g. human, Drosophila etc., together with the ability to compare these vast data sets in reasonable time frames creates the opportunity to investigate issues to do with compositional difference, genome regulation and packaging. There is great opportunity for the CRG to investigate, for example, how domestication has shaped the genomes of sheep and cattle, through comparison to ancient breeds or even ancient DNA material. We welcome expressions of interest from potential students, postdoctoral fellows and collaborators with project ideas that align to this area. (McEwan and Gemmell).
Programme 5. Reproductive and genomic tools for conservation and biocontrol
11) Reproduction and genomics for conservation
While not a major thrust of our research, the potential exists to utilise the tools and knowledge assembled in the CRG to improve outcomes for critically endangered species, such as kakapo, tuatara etc. Such work is unlikely to create great economic wealth, but it is an important component of maintaining our unique natural systems, and indeed maintaining much of what makes New Zealand the unique place that it is. The CRG is well placed to use our expertise in genetics and reproductive biology to improve the conservation outcomes for some of our most critically endangered species. We welcome expressions of interest from potential students, postdoctoral fellows and collaborators with project ideas that align to this area. (McEwan and Gemmell).
12) Reproduction and genomics for biocontrol
In the past 100 years there has been an unprecedented redistribution of species. The detection, control and eradication of unwanted species are areas of significant growth that demand new approaches and creative solutions. AgResearch has a long standing programme in place focused on the control of the brush tail possum in New Zealand. There are however opportunities for the CRG to utilise our knowledge of mammalian systems to develop tools to control and eradicate numerous other species that are problematic in New Zealand and elsewhere. These include: mice, rats, mustelids, hedgehogs etc. There are also opportunities beyond mammalian systems, with the control of insect pests, particularly those known to be the vectors of infectious disease, an area of considerable international interest. We welcome expressions of interest from potential students, postdoctoral fellows and collaborators with project ideas that align to this area. (Gemmell).
Programme 6. Genomic tools for non-classical species
AgResearch has considerable expertise in developing genetic tools and utilising these in marker assisted breeding to enhance further production traits in the sheep, cattle, dairy, and to a lesser extent deer industries. However, there are significant opportunities to use the same approach in non-classical species of economic importance (e.g. honey bees, aquaculture species etc.). We welcome expressions of interest from potential students, postdoctoral fellows and collaborators with project ideas that align to this area. (Gemmell, Wilson, Fisher, Dearden).
Programme 7. Livestock species as models for human disease
In some circumstances there are opportunities for livestock species to serve as useful models for human disease. While the maintenance of such traits in farmed systems is rare, given the sheer weight of numbers occasional individuals with mutant types of interest will be found on a seasonal basis and we are keen to exploit these opportunities to better understand the genetic basis of these defects and determine whether they may have utility in understanding similar syndromes or disease in humans. Current work in the CRG uses the possum as a model for prostate disease (Nicholson) and sheep as models of polycystic kidney disease (Eccles and McEwan).