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We are a team of scientists investigating natural products either from plants or animal venoms aiming to discover potential new drugs. We are trying to understand how chemicals interact with and change the activity of P2X receptors on cells and how drugs acting on these receptors could be used to treat a number of diseases.
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Our focus: Drug discovery for P2X receptors
The StokesLab is headed by Dr Leanne Stokes who has been working on purinergic P2X receptors for 15 years. P2X receptors are ion channels belonging to the larger family of ligand-gated ion channels. These ion channels sit in the cell membrane and receive signals from the extracellular environment to change their activity.
P2X receptors are made up of three subunits ( they are trimeric). Each subunit is arranged with 2 transmembrane domains and a large extracellular domain (cartoon picture below). The subunits are arranged as a trimer in the plasma membrane as shown by green, pink and blue coloured pieces in the cartoon. Ion channels are responsible for letting charged ions into and out of cells. These ions move through the middle of the "channel"
P2X channels are activated by the binding of their agonist, ATP to the location indicated by the black star in the cartoon drawing below. Charged cations such as sodium and calcium can then enter the cell through the P2X ion channel and this changes the activity of the cell.
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Cartoon picture of P2X receptor
3D representation of a P2X receptor structure
P2X receptors are important as new drug targets for a number of different diseases. There are 7 different types of P2X receptors; P2X7 is thought to play roles in inflammation and killing infectious organisms by changing the way immune cells work. The P2X4 receptor is thought to be involved in regulating how blood vessels dilate in response to the flow of blood. Other P2X receptors control how muscle cells contract and how neurons send their electrical signals. It is important to discover chemicals that can help us to understand how these receptors work in the body and whether they can be targeted in particular disease states where some of these processes are dysfunctional.
Research Projects:
Current projects in the lab
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Chemicals from ginseng and how they act on P2X receptors
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BBSRC-funded projects to further understand how ginsenosides act to enhance P2X receptor ion channel activity.
Drug discovery for P2X4
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Projects trying to explore animal venoms as sources of novel bio-active molecules that may act on P2X receptors. Finding new tools will help us understand how the receptors work and whether targeting them will be useful in disease.
The team:
We are a small team of scientists led by Dr Stokes with one post-doc and three PhD students
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