Investigation of novel mechanisms for the regulation of sperm-oocyte interactions. Through work with national and international collaborators, this project aims to provide unprecedented insights into how spermatozoa recognise and bind to an oocyte. The approach is based on strong preliminary data indicating that molecular chaperones play a key role in the functional remodelling of the spermatozoon by promoting the assembly of multimeric oocyte receptor complexes. Through the use of state-of-the ....Investigation of novel mechanisms for the regulation of sperm-oocyte interactions. Through work with national and international collaborators, this project aims to provide unprecedented insights into how spermatozoa recognise and bind to an oocyte. The approach is based on strong preliminary data indicating that molecular chaperones play a key role in the functional remodelling of the spermatozoon by promoting the assembly of multimeric oocyte receptor complexes. Through the use of state-of-the-art cell biology and proteomic technologies, the project aims to investigate how molecular chaperones orchestrate these changes and in doing so, improve understanding of the fertilisation cascade and open up new contraceptive strategies.Read moreRead less
Investigation of the mechanisms underlying successful placentation. The overall aim of this project is to provide novel insights into the basic cellular processes that underpin placental development and to improve our ability to manipulate mammalian reproduction, both human and animal. The placenta is critical for intrauterine development because it determines the level of nutrition, oxygenation and maternal tolerance to the developing foetus. The project intends to explore the role of prorenin ....Investigation of the mechanisms underlying successful placentation. The overall aim of this project is to provide novel insights into the basic cellular processes that underpin placental development and to improve our ability to manipulate mammalian reproduction, both human and animal. The placenta is critical for intrauterine development because it determines the level of nutrition, oxygenation and maternal tolerance to the developing foetus. The project intends to explore the role of prorenin and its receptor as a novel mechanism driving placentation. Applications for expected project outcomes may include improved breeding of threatened animal species and economically valuable domestic animals as well as improved health care and fertility control for domesticated pets and feral animals. Read moreRead less
Sensing biomechanical forces in the heart. Mechanosensitive ion channels are key molecules that define how each heart cell interacts with their physical environment. Yet how they enable cells to decode biomechanical cues remains poorly understood. At the heart of this problem is a lack of tools to quantify the force required for activation. This project aims to develop novel technologies to record the activity of these essential channels in a critical cell type within the heart, and use this inf ....Sensing biomechanical forces in the heart. Mechanosensitive ion channels are key molecules that define how each heart cell interacts with their physical environment. Yet how they enable cells to decode biomechanical cues remains poorly understood. At the heart of this problem is a lack of tools to quantify the force required for activation. This project aims to develop novel technologies to record the activity of these essential channels in a critical cell type within the heart, and use this information in addition to micro-engineering approaches to fully understand the role of these channels in force sensing and generation, at both the single cell and micro-tissue levels. This knowledge and technology has broad utility that extends far beyond cardiac biology into multiple fields.Read moreRead less
Elucidating the molecular mechanisms of dual function transporter/channels. This project aims to understand how a membrane protein that transports chemical messengers in the brain functions and how it is influenced by the membrane in which it is embedded. Cells from all life forms have a lipid membrane that separates them from their external environment. These membranes contain proteins that control the movements of molecules into and out of cells and are vital for a plethora of physiological pr ....Elucidating the molecular mechanisms of dual function transporter/channels. This project aims to understand how a membrane protein that transports chemical messengers in the brain functions and how it is influenced by the membrane in which it is embedded. Cells from all life forms have a lipid membrane that separates them from their external environment. These membranes contain proteins that control the movements of molecules into and out of cells and are vital for a plethora of physiological processes including cell-to-cell communication. The outcomes of this study will include new knowledge of this process and chemical modifiers of this transport protein. This project will benefit structural biology and biophysics training and may lead to the development of novel compounds that can be used to explore function. Read moreRead less
Determination of cellular mechanisms underpinning cancer cell metastasis through integrated in vivo imaging approaches. Understanding key steps that drive the spread of cancer is critical to improve current treatment strategies. Using cutting-edge imaging technology and in vivo model systems that mimic the disease, this project will pinpoint key events that are susceptible to drug intervention and identify new therapeutic targets.
Breaking through the Gram-negative cell barrier. This project aims to develop fundamental knowledge of the cell envelope in Gram-negative bacteria, which functions as a permeability barrier to small molecules. Combining innovative functional genomics with biochemistry, this project will determine how small molecules can pass across the cell envelope, and the chemical properties that they need to do so. Some Gram-negative bacteria are human pathogens and cause serious infections, whereas others a ....Breaking through the Gram-negative cell barrier. This project aims to develop fundamental knowledge of the cell envelope in Gram-negative bacteria, which functions as a permeability barrier to small molecules. Combining innovative functional genomics with biochemistry, this project will determine how small molecules can pass across the cell envelope, and the chemical properties that they need to do so. Some Gram-negative bacteria are human pathogens and cause serious infections, whereas others are used in biotechnology for biosynthetic chemical production or bioremediation. This project expects to help the future development of new antibiotics and assist in the design of strains to be used in biotechnological applications.Read moreRead less
A Generic Solution for Interfacing Electrodes with Biological Media. Electrodes are the critical element of stimulating implantable devices such as cardiac pacemakers, bionic eyes and cochlear implants, the most commercially successful biosensors, and are emerging as key to new technologies for testing new drug leads using cells. In all these applications of electrodes in biology there has never been a solution to stopping unwanted adsorption of biological material onto the electrode that does ....A Generic Solution for Interfacing Electrodes with Biological Media. Electrodes are the critical element of stimulating implantable devices such as cardiac pacemakers, bionic eyes and cochlear implants, the most commercially successful biosensors, and are emerging as key to new technologies for testing new drug leads using cells. In all these applications of electrodes in biology there has never been a solution to stopping unwanted adsorption of biological material onto the electrode that does not dramatically decrease electrode performance. The proposed research finally provides a solution via surface modification. This strategy will enhance the performance of all the devices above and will open doors to new applications of electrochemistry within biology.Read moreRead less
Nuclear and chromatin architecture in the replication stress response. DNA replication is an essential biological activity required for the transmittance of genomic material across cell divisions. If errors occur during DNA replication, this results in dangerous outcomes including mutation, genome instability, and cell death. Cells cope with challenges to DNA replication through a process called the replication stress response. This fellowship explores a newly discovered pathway in the replicati ....Nuclear and chromatin architecture in the replication stress response. DNA replication is an essential biological activity required for the transmittance of genomic material across cell divisions. If errors occur during DNA replication, this results in dangerous outcomes including mutation, genome instability, and cell death. Cells cope with challenges to DNA replication through a process called the replication stress response. This fellowship explores a newly discovered pathway in the replication stress response where changes to the architecture of a cell nucleus, and movement of the genomic material inside, promotes repair of genomic damage that occurs during replication. The result of this project will be an understanding of fundamental biological processes that protect human genomes.Read moreRead less
Biomimetic surface coatings for drag and fouling reduction. This project aims to provide new insights into liquid flow and adsorption at liquid/solid and liquid/liquid interfaces, by using a combination of theoretical predictions, nanoscale techniques and nanofabrication approaches. Expected outcomes are the development of liquid-repellent slippery surface coatings that reduce hydrodynamic drag and inhibit marine fouling. This will benefit the fields of advanced manufacturing and smart coatings, ....Biomimetic surface coatings for drag and fouling reduction. This project aims to provide new insights into liquid flow and adsorption at liquid/solid and liquid/liquid interfaces, by using a combination of theoretical predictions, nanoscale techniques and nanofabrication approaches. Expected outcomes are the development of liquid-repellent slippery surface coatings that reduce hydrodynamic drag and inhibit marine fouling. This will benefit the fields of advanced manufacturing and smart coatings, and will underpin a wide range of energy efficient processes and products. Slippery coatings will solve urgent environmental problems of social value by improving the energy and chemical efficiency in fluid flow, heat transfer, secondary oil recovery, microfluidics, and anti-fouling.Read moreRead less
Vesicles stabilised by compressed carbon dioxide as nanoreactors and templates for radical polymerisation. A new environmentally friendly method for synthesis of surfactant vesicles involving stabilisation using low pressure carbon dioxide will be applied to the synthesis of hollow polymeric nanoparticles and polymer of well-defined structure. The resulting polymeric structures will have applications in drug delivery and nano-engineered materials.