Nuclear RNA surveillance and its connection to splicing quality control. Due to the error-prone nature of RNA splicing, elaborate quality control processes ensure that only correctly spliced transcripts can leave the nucleus. It has long been known that incorrectly spliced mRNA transcripts are degraded by the nuclear RNA surveillance machinery, but how the RNA quality control machinery is connected to nuclear RNA surveillance is not known. This proposal aims to uncover the connection between the ....Nuclear RNA surveillance and its connection to splicing quality control. Due to the error-prone nature of RNA splicing, elaborate quality control processes ensure that only correctly spliced transcripts can leave the nucleus. It has long been known that incorrectly spliced mRNA transcripts are degraded by the nuclear RNA surveillance machinery, but how the RNA quality control machinery is connected to nuclear RNA surveillance is not known. This proposal aims to uncover the connection between these two important processes and will fill a significant gap in our understanding of how splicing quality control and nuclear RNA surveillance work. The project will also identify sequence features that trigger abortive splicing reactions and will thus help to improve the design of synthetic mRNAs.Read moreRead less
Role of R-loops and double R-loops in genome organisation and transcription. The majority of our genome is converted to an extensive network of non-protein-coding RNA molecules (ncRNAs), but the function of these ncRNAs is unknown. This project aims to identify and determine the mechanism of action of nuclear ncRNA networks with a particular focus on nuclear ncRNAs that form RNA-DNA hybrids with the genomic DNA. These studies have the potential to lead to ground-breaking discoveries in our under ....Role of R-loops and double R-loops in genome organisation and transcription. The majority of our genome is converted to an extensive network of non-protein-coding RNA molecules (ncRNAs), but the function of these ncRNAs is unknown. This project aims to identify and determine the mechanism of action of nuclear ncRNA networks with a particular focus on nuclear ncRNAs that form RNA-DNA hybrids with the genomic DNA. These studies have the potential to lead to ground-breaking discoveries in our understanding of genome organisation and the mechanism of transcription control, and might provide an entirely new tool-box to manipulate genome function. This should provide significant benefits to efforts to develop innovative biotechnology and genome editing technologies in plants and animals.Read moreRead less
RNA surveillance and the initial steps of RNA biogenesis. This project aims to understand the initial steps of RNA biogenesis and how this process is linked to the chromatin environment. Although less than five per cent of our genome encodes proteins, almost the entire genome is transcribed to RNA. A large portion of these transcripts are degraded during the early steps of RNA biogenesis by the RNA surveillance machinery, but the mechanism for the recognition and degradation of these transcripts ....RNA surveillance and the initial steps of RNA biogenesis. This project aims to understand the initial steps of RNA biogenesis and how this process is linked to the chromatin environment. Although less than five per cent of our genome encodes proteins, almost the entire genome is transcribed to RNA. A large portion of these transcripts are degraded during the early steps of RNA biogenesis by the RNA surveillance machinery, but the mechanism for the recognition and degradation of these transcripts is not understood. New evidence suggests that the chromatin environment of the transcribed locus plays an important role in this process. This project will lead to significant benefits in the implementation of emerging RNA-based technologies and in understanding how genome stability is maintained.Read moreRead less
How and why cells decorate their genetic messages. This project aims to investigate a new layer of genomic control mediated not by DNA but instead by chemical modifications found on the cell's working copies of genetic information called messenger RNA. The investigations will use cutting-edge RNA sequencing technology and the fruit fly model organism to uncover the scope and mechanisms by which such modifications enact their roles at the molecular level and within the body plan of an animal. Exp ....How and why cells decorate their genetic messages. This project aims to investigate a new layer of genomic control mediated not by DNA but instead by chemical modifications found on the cell's working copies of genetic information called messenger RNA. The investigations will use cutting-edge RNA sequencing technology and the fruit fly model organism to uncover the scope and mechanisms by which such modifications enact their roles at the molecular level and within the body plan of an animal. Expected outcomes include novel molecular tools and models that will assist in understanding and manipulating the function of genomes. Such knowledge should provide benefits in developing innovative biotechnology applications of use in human health, agriculture and managing the environment.
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How novel ribosomal RNA gene repeat variants drive cellular function. The hundreds of ribosomal RNA gene repeat copies are a remarkable part of our genomes, as they encode the machinery responsible for all cellular protein synthesis and shape the structure of the nucleus. However, due to their high degree of sequence similarity, they still have not been assembled into the human genome reference. This project will resolve this impasse and furthermore uncover the functional impacts of a newly iden ....How novel ribosomal RNA gene repeat variants drive cellular function. The hundreds of ribosomal RNA gene repeat copies are a remarkable part of our genomes, as they encode the machinery responsible for all cellular protein synthesis and shape the structure of the nucleus. However, due to their high degree of sequence similarity, they still have not been assembled into the human genome reference. This project will resolve this impasse and furthermore uncover the functional impacts of a newly identified molecular diversity in the ribosomal RNA gene repeats. Outcomes include new paradigms for how the ribosomal RNA gene repeats drive protein synthesis and genome structure, and a blueprint to develop novel genomics applications for human health, biotechnology, and agriculture.Read moreRead less
The roles and regulators of new plant cells linked to root transport. Plant genomics has moved to the single cell resolution, allowing precise investigations of previously hidden cell types and cell states that respond to environmental stress and that vary among differentially adapted plant populations. Here, we will extend our pioneering efforts that have mapped and discovered novel root cell types, to determine their salt and nutrient stress responses, and to elegantly dissect the underling ca ....The roles and regulators of new plant cells linked to root transport. Plant genomics has moved to the single cell resolution, allowing precise investigations of previously hidden cell types and cell states that respond to environmental stress and that vary among differentially adapted plant populations. Here, we will extend our pioneering efforts that have mapped and discovered novel root cell types, to determine their salt and nutrient stress responses, and to elegantly dissect the underling causal genetic variation. The unique cell markers and regulatory networks will be validated with tissue specific and transgenic tools that can work across a host of plant species to reveal adaptive cellular responses to harsh environmental conditions.Read moreRead less
Regulators of protein translation reveal new pathways to plant productivity. This proposal aims to make transformative insights into the control of photosynthetic protein production. Photosynthesis is a key target for crop improvement that can address global food security. Improving photosynthesis requires precision control of photosynthetic proteins. It was unknown how this is achieved at the level of protein production. Excitingly, the team discovered how cellular protein production changes in ....Regulators of protein translation reveal new pathways to plant productivity. This proposal aims to make transformative insights into the control of photosynthetic protein production. Photosynthesis is a key target for crop improvement that can address global food security. Improving photosynthesis requires precision control of photosynthetic proteins. It was unknown how this is achieved at the level of protein production. Excitingly, the team discovered how cellular protein production changes in response to photosynthetic demand. The project strives to uncover how clusters of RNAs are decayed or translated into new proteins based on RNA features and linked binding proteins. This will allow manipulation of the accumulation of target proteins towards the goal of revealing unexplored ways to improve photosynthesis.Read moreRead less
Does coevolution drive speciation? This project aims to connect micro-evolutionary processes with macro-evolutionary patterns to test the extent to which tightly coupled co-evolutionary interactions between species drive evolutionary diversification. The project will use techniques including the most recent phylogenetic modelling methods, field experiments and molecular genetics. Expected outcomes include advancing understanding of the mechanisms that generate biodiversity and developing new tec ....Does coevolution drive speciation? This project aims to connect micro-evolutionary processes with macro-evolutionary patterns to test the extent to which tightly coupled co-evolutionary interactions between species drive evolutionary diversification. The project will use techniques including the most recent phylogenetic modelling methods, field experiments and molecular genetics. Expected outcomes include advancing understanding of the mechanisms that generate biodiversity and developing new techniques for acquisition of DNA from museum specimens. The project is expected to provide significant benefits, such as insights into the processes that promote new species in nature.Read moreRead less
Optimising the spring in your step to enhance footwear design. This project aims to examine how the nervous system adjusts the mechanical function of our feet across a spectrum of speeds, from slow running through to maximal effort sprinting. The proposed research will explore how the nervous system controls the function of the foot to meet the ever-varying demands of locomotion in the real-world. Expected outcomes of this project are to determine if running shoes help or hinder the natural spri ....Optimising the spring in your step to enhance footwear design. This project aims to examine how the nervous system adjusts the mechanical function of our feet across a spectrum of speeds, from slow running through to maximal effort sprinting. The proposed research will explore how the nervous system controls the function of the foot to meet the ever-varying demands of locomotion in the real-world. Expected outcomes of this project are to determine if running shoes help or hinder the natural spring-like function of the foot. It will explain a conceptually novel design allowing shoes to support our feet, whilst harnessing the energetic benefits of the foot's spring-like function. This research has the potential to revolutionise athletic footwear design and has direct implications for enhanced performance in running athletes.Read moreRead less
Growing up to be supersonic: bat echolocation origins and mechanics. This project aims to address the unresolved evolutionary origins of bat echolocation. Using a unique combination of development, evolution and novel engineering testing, this project expects to generate new insights into how features of the skull have evolved to allow bats to use their senses to interact with the environment. Expected outcomes include the identification of skull features that are unique to echolocating bats and ....Growing up to be supersonic: bat echolocation origins and mechanics. This project aims to address the unresolved evolutionary origins of bat echolocation. Using a unique combination of development, evolution and novel engineering testing, this project expects to generate new insights into how features of the skull have evolved to allow bats to use their senses to interact with the environment. Expected outcomes include the identification of skull features that are unique to echolocating bats and tests of how these relate to the frequency and detection range of sounds produced. Benefits include improved conservation planning for urban and rural bat populations, and potential commercial advances through engineering applications that mimic the biological process of echolocation. Read moreRead less