Verification of a theoretical model of the dynamical genesis of brain electrical activity. The physiological basis for the rhythmic scalp electrical activity known as the alpha rhythm has remained elusive despite being first recorded over eighty years ago. However, one of the applicants (DTJL) has developed a novel theory of the electroencephalogram (EEG) that theoretically articulates the necessary physiological conditions required for the genesis of this activity that is subject to rigorous e ....Verification of a theoretical model of the dynamical genesis of brain electrical activity. The physiological basis for the rhythmic scalp electrical activity known as the alpha rhythm has remained elusive despite being first recorded over eighty years ago. However, one of the applicants (DTJL) has developed a novel theory of the electroencephalogram (EEG) that theoretically articulates the necessary physiological conditions required for the genesis of this activity that is subject to rigorous experimental test. Empirical verification of this theory will pave the way to elucidating the functional importance of large scale brain electrical activity in neural information processing as well as enabling the rational use of the EEG for drug design and diagnosis.Read moreRead less
Biomolecular activity modulated by interaction with nanostructures. Nanotechnological methods are able to reliably fabricate artificial nanostructures with dimensions similar to those of large biomolecules (a few to tens of nanometers). This study focuses on the interaction of artificial nanostructures with biomolecules such as proteins and DNA, and will enable scientists to better understand biomolecular recognition and binding events, which are central to all biological processes. The underst ....Biomolecular activity modulated by interaction with nanostructures. Nanotechnological methods are able to reliably fabricate artificial nanostructures with dimensions similar to those of large biomolecules (a few to tens of nanometers). This study focuses on the interaction of artificial nanostructures with biomolecules such as proteins and DNA, and will enable scientists to better understand biomolecular recognition and binding events, which are central to all biological processes. The understanding gained can then be used to design biomimetic surfaces for use in health monitoring and medical diagnostic devices with improved sensitivity, robustness and portability, thereby providing significant benefits to the health sector.Read moreRead less
Physiology of oxygen transport in the mammalian kidney. This project aims to improve understanding of oxygen regulation in renal tissue and knowledge of the physiology of the kidney. The mammalian kidney receives more oxygen than it uses or needs, and yet renal tissue is commonly found to be hypoxic. This project proposes that oxygen transport to the renal tissue is limited by blood vessel surface area. The project expects to generate anatomical data currently missing from the renal physiology c ....Physiology of oxygen transport in the mammalian kidney. This project aims to improve understanding of oxygen regulation in renal tissue and knowledge of the physiology of the kidney. The mammalian kidney receives more oxygen than it uses or needs, and yet renal tissue is commonly found to be hypoxic. This project proposes that oxygen transport to the renal tissue is limited by blood vessel surface area. The project expects to generate anatomical data currently missing from the renal physiology community, and potentially change the accepted story of oxygen homeostasis in the kidney. This will provide significant benefits, such as the provision of the foundational physiological science behind a determinant of kidney health and its flow-on impact to quality of life.Read moreRead less
The Role of C-kit and Selected TGF beta Family Members in Recruitment. The recruitment of primordial follicles into the growth phase is central to female reproductive function, however the control of this process to date, has been poorly understood due to inadequate technologies. Our team has recently developed novel recruitment models and a new and innovative method of isolating primordial follicles which will enable us to identify the role of c-kit and selected TGF beta family members in recru ....The Role of C-kit and Selected TGF beta Family Members in Recruitment. The recruitment of primordial follicles into the growth phase is central to female reproductive function, however the control of this process to date, has been poorly understood due to inadequate technologies. Our team has recently developed novel recruitment models and a new and innovative method of isolating primordial follicles which will enable us to identify the role of c-kit and selected TGF beta family members in recruitment. This work will provide cornerstone scientific knowledge about the control of female reproduction and provide the impetus for the development of more effective contraception and superovulation strategies in mammals.Read moreRead less
Oxidative stress-induced alterations of the host erythrocyte by the malaria parasite. The malaria parasite spends part of its lifecycle inside the red blood cells of its host. During this time, the parasite modifies many of the features of the red blood cell and subjects it to high levels of oxidative stress. We will use and develop a variety of fluorescence and microscopic techniques to understand the molecular basis of the alterations in the organization of membrane proteins in malaria parasit ....Oxidative stress-induced alterations of the host erythrocyte by the malaria parasite. The malaria parasite spends part of its lifecycle inside the red blood cells of its host. During this time, the parasite modifies many of the features of the red blood cell and subjects it to high levels of oxidative stress. We will use and develop a variety of fluorescence and microscopic techniques to understand the molecular basis of the alterations in the organization of membrane proteins in malaria parasite-infected red blood cells. We will examine the roles of oxidative stress and of parasite proteins in modulating the properties of the host cell membrane.Read moreRead less
Probing membrane rafts using surface-selective multi-dimensional microscopy. The results of this project will provide fundamental insights into the role played by domains in cell membranes in the regulation of membrane protein function. These insights will create new avenues in the biotechnology industry for development of novel therapeutics aimed at disruption of membrane protein-protein interactions that cause aberant cell signalling in disease states such as cancer.
Advanced high resolution atomic force microscopy of biomolecules in physiological environments. The proposed research is intended to explain high resolution bioimaging problems addressed only phenomenologically before. A correct physical model would help the scientific community to optimise imaging of dynamic biological systems, extending our knowledge about the way living organisms function. With dynamic bioimaging, the mechanism of certain diseases such as Alzheimer's - where biomolecule fiber ....Advanced high resolution atomic force microscopy of biomolecules in physiological environments. The proposed research is intended to explain high resolution bioimaging problems addressed only phenomenologically before. A correct physical model would help the scientific community to optimise imaging of dynamic biological systems, extending our knowledge about the way living organisms function. With dynamic bioimaging, the mechanism of certain diseases such as Alzheimer's - where biomolecule fiber formation plays a key role - can also be addressed, thus the project has even therapeutical relevance. Furthermore, adequate description of liquid phase imaging can help engineers in the design of better hardware and software solutions, for the benefit of the bio-nanotechnological industry.Read moreRead less
Probing the function of protein molecular motors on nano-fabricated structures. The function of protein linear molecular motors, which are natural dynamic bio-nano-devices with a ubiquitous importance in multicellular organisms, will be 'probed' with purposefully designed nano-structures fabricated via photo- or Scanning Probe Microscopy Lithography, that is, flat polymeric surfaces with combinatorial combinations of physico-chemistries; and micro/nano-channels and nano-wells with critical dimen ....Probing the function of protein molecular motors on nano-fabricated structures. The function of protein linear molecular motors, which are natural dynamic bio-nano-devices with a ubiquitous importance in multicellular organisms, will be 'probed' with purposefully designed nano-structures fabricated via photo- or Scanning Probe Microscopy Lithography, that is, flat polymeric surfaces with combinatorial combinations of physico-chemistries; and micro/nano-channels and nano-wells with critical dimensions similar to the scale of the probed biomolecules. The project turns 'up-side down' the challenge of invasive nano-probing of biomolecules using it in an engineered manner. The fundamental understanding of linear molecular motors will impact on biomedical science and on the assessment of hybrid natural-artificial dynamic nano-devices.Read moreRead less
A microfluidic approach to study the mechanobiology of ageing blood vessels. This project aims to study the effect of the stiffening of ageing arteries in endothelial cells. It explores the changes that occur in endothelial cells using a unique microfluidic technology with tuneable wall stiffness to mimic the biophysical and biochemical properties of ageing arteries. The expected outcome is the identification of the cellular mechanisms that control endothelial responses to arterial stiffening. T ....A microfluidic approach to study the mechanobiology of ageing blood vessels. This project aims to study the effect of the stiffening of ageing arteries in endothelial cells. It explores the changes that occur in endothelial cells using a unique microfluidic technology with tuneable wall stiffness to mimic the biophysical and biochemical properties of ageing arteries. The expected outcome is the identification of the cellular mechanisms that control endothelial responses to arterial stiffening. This should provide the fundamental knowledge required to assist in the development of new therapies to tackle age-related conditions such as cardiovascular disease and dementia.Read moreRead less
The comparative physiology of oxygen delivery to the kidney. The kidney is in danger of hyperoxia because the kidney receives so much blood relative to its mass. It is proposed that shunting oxygen between arteries and veins substantially mitigates the risk of hyperoxia, but under certain circumstances shunting substantially increases the risk of kidney hypoxia. Using a combination of synchrotron and histological imaging, This project will carefully define the three-dimensional vasculature of th ....The comparative physiology of oxygen delivery to the kidney. The kidney is in danger of hyperoxia because the kidney receives so much blood relative to its mass. It is proposed that shunting oxygen between arteries and veins substantially mitigates the risk of hyperoxia, but under certain circumstances shunting substantially increases the risk of kidney hypoxia. Using a combination of synchrotron and histological imaging, This project will carefully define the three-dimensional vasculature of the renal cortex in several different species and interpret its functional significance using computational modeling. The outcome of this project will be a new understanding in the comparative physiology of oxygen transport and shunting in the kidney.Read moreRead less