- Training for expertise in multiomics approaches to study biological processes that have eluted scientist until now.
- A unique animal model system that provides opportunities to explore the (environmental) condition dependency of developmental programmes and life-history (phenotypic plasticity).
- A multidisciplinary learning environment that includes comparative and functional genomics, bioinformatics and machine learning, stress biology and evolution, cell biology and development.
Diapause is a natural process by which an organism enters a state of suspended animation in response to environmental challenges. Diapause is unique from other dormancies (e.g. quiescence) as the stage, entry and length of developmental arrest is endogenously programmed in advance of onset, and may be either facultative or obligatory. The environmental genomics model organism Daphnia produces diapausing embryos as part of its reproductive cycle. When buried in the lake sediments, these embryos produce a living archive of past populations that can be sampled and resuscitated in the laboratory after prolonged periods of time. Investigators at the University of Birmingham have hatched these dormant embryos to resume development, producing healthy reproductive adults, even after 700 years of sustained developmental arrest. From these hatchlings, populations of Daphnia that are native to Europe and to North America are indefinitely maintained in the laboratory for evolutionary studies through 10,000 generations. Our work at co-advising a student (Ms Rosemary Barnett who is now submitting her thesis) discovered that the development of embryos destined to diapause is delayed compared to non-diapausing embryos until arrested, after roughly eleven rounds of cellular divisions (over 3500 cells) whereupon mitotic activity is absent, cytoskeletal components are depleted and cells are condensed for these exceptionally long periods of metabolic inertness. Her analysis by statistical machine learning of a multiomics datasets comparing the developmental programmes of both types of embryos, revealed both recognizable and newly discovered regulatory pathways, having significant implications on our understanding of the plasticity of developmental programmes towards two extreme life-history stages, and how life can be suspended for centuries of environmental hardship.
This next CENTA PhD Project Proposal follows upon these initial molecular biological findings from observing the entry into diapause, to now discover the process by which a diapausing embryo “senses” environmental cues to subsequently resume development. The student will investigate the degree to which diapausing embryos are reactive to environmental signals and perturbations as a function of time at dormancy, and whether the breaking of diapause consists of a reversal of molecular and cellular events that had earlier prepared the embryos for suspended animation.
Our earlier technological multiomics approach of simultaneously measuring transcriptomics and metabolomics will now be supplemented with epigenomic measurements of chromatin dynamics and transcription, gene silencing/activation, cell cycle progression, apoptosis and differentiation. The student will be employing new approaches for integrated multiomics of single cells and low-input genome samples that were pioneered at the Earlham Institute. Decades of ecological work points to a strong genetic basis for the natural variation that is observed in Daphnia’s life-history responses to changes in photoperiod, temperature, crowding and nutrition. The student will also access an “evolutionary genetic” panel consisting of populations resuscitated from a lake sediment spanning 100 years of ecological change affecting all of these ecological parameters (including light attenuation in the water column) to then associate the variation observed in the biomolecular pathways controlling diapause to the variation in these ecological parameters under controlled experimental conditions.
Training and Skills
The student will be trained in modern molecular biological techniques that have revolutionized biosciences when applied to biomedical research, and now applied to environmental research. The student will receive training in stress and systems biology, specializing in the academic discipline called ecological and evolutionary genomics. The student will develop practical skills in genomics, transcriptomics, metabolomics, epigenomic and bioinformatics, including an important class of machine and deep learning techniques called “explainable artificial intelligence”. Finally, the student will become an expert in the use of model species for the study of biological processes that are generally important to advance the environmental sciences.
Year 1: The student will undertake a phenotypic screen of the evolutionary genetic panel spanning 100 years to measure the distribution in responsiveness to environmental cues that break diapause. The phenotypes will be associated with the documented genomic DNA and functional genomic variation. The anticipated result is (1) measurement of the distribution of phenotypes interpreted in light of ecological change, (2) list of candidate loci and pathways that are identified by statistical genetics and (3) identity of the experimentally trackable genotypes for further study.
Year 2: The student will carry out a controlled experiment that collects and analyses diapausing embryos are fine-scale time intervals in their processes of receiving, processing and responding to environmental perturbations, including cues that break diapause. These will be processed using a variety of omics techniques listed above. The interpretation of the data will be made in light of testing whether the breaking of diapause consists of a reversal of molecular and cellular events that had earlier prepared the embryos for suspended animation. The anticipated result is understanding (1) the persistence of metabolic processes throughout diapause, (2) the responsiveness of diapausing embryos to environmental challenges versus evolved cues for a life-history switch from the environment, (3) the process by which development is resumed from diapause, and whether this process is time independent.
Year 3: The student will integrate the phenotypic and multiomics data by machine learning approaches to discover the genomic, epigenomic, metabolic and biomolecular pathways that regulate suspended animation.
The ambitious proposed work is made possible over 3-4 years by the ongoing resources and data developed by NATURAL ENVIRONMENT RESEARCH COUNCIL, highlight topic: Breaking the code of adaptive evolution, which ends in 2020.
Partners and collaboration (including CASE)
This project is closely associated with other research at the University of Birmingham and beyond that focuses on the study of diapausing Daphnia populations buried in lake sediments so to uniquely witness the molecular mechanisms of adaptive evolution in natural populations over decades and centuries against the documented environmental changes that have occurred from local to regional scales (called resurrection biology). As such, partners and collaborators include the Natural History Museum (ancient DNA research), the UK MetOffice (climate change), Natural England and the Environment Agency (biodiversity in the face of pollutants).
Any questions about the project can be directed to:
Professor John Colbourne
Chair of Environmental Genomics
School of Biosciences,
University of Birmingham