Dr Amy Cherry is a Senior Lecturer in 生物化学 在U2电竞体育平台. 在这个学术博客中, she explores how proteins perform a diverse range of roles within our cells 而且 her research around the structure 而且 function of proteins involved in the Hedgehog signalling pathway. Cherry博士也是 Worcester Biomedical 研究 Group (WBRG).         

 

A glance along the confectionary shelf of any supermarket tells you how aware we have become of the importance of protein for human health. Whereas 1950s Mars Bar adverts promoted the health benefits of glucose, in 2016 Mars jumped into the protein supplementation trend with the introduction of the Mars HiProtein bar. In 2021 the global protein supplements market was valued at 20.47 billion USD, but what does the average consumer know about the roles of proteins in our body? 

The first myth that I would like to dispel is that protein is a single entity. 事实上, the Human proteome organisation (HUPO) records show evidence for the existence of 18,407年人类蛋白质, 到目前为止. 蛋白质数据库, which is the repository for all protein structures which have been solved, contained 193455 records at the time of writing.

So why are we so interested in solving protein structures? Well, proteins perform a diverse range of roles within our cells. Most people are aware that proteins are important for muscle strength. There are in fact two different proteins which drive muscle contraction; actin which forms rope-like structures attached to the ends of the cells 而且 myosin, which acts like a line of men pulling the rope so that the ends of the cell are pulled together causing it to contract. 然而, other proteins are also needed to make this happen. Chemical energy is needed to drive the contraction. This is provided by networks of enzymes (made of protein) which break down our food to release energy. We don’t want our muscle cells to be contracting all the time, 另一种调节蛋白, 肌钙蛋白, covers the “h而且holds” on the rope when not in use. 肌钙蛋白 will release the “h而且holds” when calcium enters the cell through ion channels which are also protein molecules. 

Since our proteins have such vital roles in our cells, when they are functioning incorrectly, 或者根本没有, this can lead to many different diseases. Diabetes mellitus is caused by a lack of the protein hormone insulin 而且 haemophilia A is caused by a lack of one of the blood clotting proteins factor VIII.  相反, cancers are often caused by an increase in activity of proteins which send messages to the cell telling it to replicate.

With this knowledge we can develop treatments for these diseases. Insulin was first administered to patients with diabetes mellitus 100 years ago. 然而, by learning about the protein structure, scientists have been able to develop a modified version named Lispro in which the building blocks have been slightly rearranged to alter its stability. This engineered form of the protein has a more predictable action profile which produces more reliable outcomes in patients. Therapeutic factor VIII has been modified even more dramatically. The gene for factor VIII has been joined to the gene for another very stable protein. The resulting fusion protein is not degraded as rapidly as st而且ard factor VIII 而且 hence, haemophiliacs don’t need to administer the drug as often.  

 

A diagram of two different str而且s of insulin the left being native insulin 而且 the right being modified insulin lispro

My own research focusses on the structure 而且 function of proteins involved in the Hedgehog signalling pathway, a communication network which is overactive in many forms of cancer. Drugs developed to inhibit the receptor protein which receives the first chemical message in this network have been used successfully to treat cancer patients. My work has shown how the final activator protein GLI, is repressed by interaction with a suppressor protein SUFU. We are now investigating other proteins which alter this interaction sincethey may also prove to be viable drug targets.

A diagram of a Hedgehog signalling pathway

 

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