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An introduction to Research | Current research funded by CLDF | Characterisation of the role of VPS33B in polarised protein trafficking in liver cells
Characterisation of the role of VPS33B in polarised protein trafficking in liver cells
Dr Paul Gissen - Institute of Biomedical Research, The Medical School, University of Birmingham ARC syndrome is a severe inherited disease affecting newborn children that causes abnormally functioning liver and other organs. Most patients with ARC develop jaundice, fail to thrive and die in the first year of life. No treatment is available for these children. Recently we found that genetic defects (mutations) in the VPS33B gene cause ARC syndrome. Although the exact of how the defects in VPS33B (the protein encoded by the VPS33B gene) causes the liver disease, we have found that it prevents the transport of other proteins inside liver and kidney cells to their correct destination. We wish to determine how the gene abnormality in ARC affects the transport of proteins in the liver cells and cause severe liver disease. 1. We will grow specialised liver cells in culture. These cells have a particular characteristic in that they maintain their polarity (polarised cells). This term means that the cell’s outer coat (cell membrane) has different functions depending on whether it is on the top, side or bottom of the cells. The specific function of the cell membrane is performed by membrane proteins. These proteins are manufactured inside the cell and then transported to the membrane by the process called protein trafficking. 2. In this project we will study protein trafficking using a specialised type of microscopy (confocal microscopy). 3. We will identify other proteins, whose absence may cause similar abnormalities to those seen with the inactivation of VPS33B. This analysis will help to clarify the disease mechanism behind ARC syndrome. 4. Once we can assess polarised transport in the liver cells, we will perform studies in the liver cells from patients with other childhood liver diseases. This will help in understanding the role of polarised protein transport in causing disease, and may suggest new methods of treatment for these diseases. Budget:
| Year I | Year II | Year III | Total | Stipend | £15,500 | £16,300 | £17,100 | £48,900 | Fees | £3,200 | £3,300 | £3,400 | £9,900 | Consumables | £5,000 | £5,000 | £5,000 | £15,000 | TOTAL COSTS | £23,700 | £24,600 | £25,500 | £73,800 |
Project: 36 Months
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