Cloning Of Human NK Cells And Macrophages Carbohydrate Receptors
Funder
National Health and Medical Research Council
Funding Amount
$489,750.00
Summary
Lymphocytes, also known as white blood cells, are important for the well being of all individuals as these are the cells which fight infection by microorganisms. The lymphocyte gets its information about enviroment and communicates with other cells using molecules on the cell surface. We are examining a group of molecules found on the surface of different lymphocytes which bind different sugars, and also to characterised new cell surface molecules that interact with carbohydrates. These studies ....Lymphocytes, also known as white blood cells, are important for the well being of all individuals as these are the cells which fight infection by microorganisms. The lymphocyte gets its information about enviroment and communicates with other cells using molecules on the cell surface. We are examining a group of molecules found on the surface of different lymphocytes which bind different sugars, and also to characterised new cell surface molecules that interact with carbohydrates. These studies will examine the structure of the the molecules that interact with with sugars, in order to understand how these give messages to the lymphocyte to trigger various functions that these cell perform in the immune response. We will isolate the genes for these and study their function in greater detail. The cell surface carbohydrate receptors represents several different families of molecules, it is highly likely that these have important roles in the immune response. The potential significance of studying these lymphocyte cell surface molecules is in defining the functional properties of these molecules, the results of which will give us novel insights into the molecular mechanisms involved in the generation of immune responses, the mechanism of immuno deficiency and autoimmunity.Read moreRead less
Signalling Of Muscle Force By Golgi Tendon Organs During Exercise And Fatigue
Funder
National Health and Medical Research Council
Funding Amount
$181,320.00
Summary
It is a common experience for objects being carried to feel heavier and tasks needing muscular effort to become more difficult as one becomes tired and the muscles fatigue during exertion. The sensation of muscle force depends on two factors. One, a sense of the effort required to perform a task, is generated in the central nervous system and. The other, a sense of the force actually developed by the muscles, is generated in the muscles themselves by signals from sensory receptors called Golgi t ....It is a common experience for objects being carried to feel heavier and tasks needing muscular effort to become more difficult as one becomes tired and the muscles fatigue during exertion. The sensation of muscle force depends on two factors. One, a sense of the effort required to perform a task, is generated in the central nervous system and. The other, a sense of the force actually developed by the muscles, is generated in the muscles themselves by signals from sensory receptors called Golgi tendon organs. The sensation of muscle force and the heaviness of objects results from a combination of both senses, but the contribution of each is unknown. The aim of the project is to determine whether the disturbance of force sense in fatigued muscles results from changes in the way tendon organs signal the actual force developed by the muscles. This will be important for understanding how force sense is disturbed following exercise and in disease states, and for understanding the normal way muscle force is sensed in everyday situations. Disturbances of force sense after exercise will be documented in human subjects by asking them to generate what they perceive to be equal forces in both arms or legs, before and after one limb only is exercised. Errors in force estimation will show up as mismatches between the two limbs. The difficulty with human experiments is that the signals generated by tendon organs cannot be measured directly, but only inferred, perhaps wrongly. This difficulty will be overcome by measuring tendon organ activity directly in anaesthetised animals, where the muscles will be electrically stimulated to perform exercise similar to that in the human experiments. A change in tendon organ signalling will be taken to mean that similar changes in humans could be responsible for disturbances of force sense. In further experiments, the mechanism of the changes will be explored.Read moreRead less
Structure-function Studies Of Ion Permeation And Selectivity In Recombinant Glycine Receptor Channels
Funder
National Health and Medical Research Council
Funding Amount
$331,300.00
Summary
Ligand-gated ion channels (LGICs) are members of a superfamily of receptor channels, with very significant structural and functional similarities, which play a major role in fast synaptic neurotransmission within the brain and spinal cord, and underlying the complex behaviour of the nervous system, but when dysfunctional can result in major neurological problems. Glycine is one of the two most important inhibitory neurotransmitters in the central nervous system. Impaired glycine-mediated neurotr ....Ligand-gated ion channels (LGICs) are members of a superfamily of receptor channels, with very significant structural and functional similarities, which play a major role in fast synaptic neurotransmission within the brain and spinal cord, and underlying the complex behaviour of the nervous system, but when dysfunctional can result in major neurological problems. Glycine is one of the two most important inhibitory neurotransmitters in the central nervous system. Impaired glycine-mediated neurotransmission underlies a range of inherited neurological diseases and already, it has been shown that the human disorder, familial Startle disease (hyperekplexia) occurs because of point mutations that have impaired the permeation and activation of the glycine receptor (GlyR). Similarly, certain epilepsies are now known to be caused by mutations in, or close to, the channel region in the excitatory acetylcholine receptors (AChRs), which affect channel activation and ion permeation. However, because of their very significant structural and functional similarities, information obtained in one member of the LGIC family of receptors has strong potential application to the other members and the GlyR with its simpler structure has certain advantages for investigation. The first aim of this project is to investigate how the molecular biological structure of these ion channels controls permeation, how it affects how different ions are selectively allowed to move through it and how it affects channel activation. A second related aim is to learn more about the process of desensitization of GlyR receptors, whereby a sustained presence of a high concentration of agonist can cause a reduction in receptor response. A third aim is to specifically investigate the mechanisms underlying the mode of molecular disruption resulting from two new Startle disease mutations, which, in addition to their own inherent clinical value, can also give general information about receptor function.Read moreRead less