07.09.2018 change 07.09.2018

Wrocław scientists modify human protein for use in therapy

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Wrocław scientists are working on modifications of one a human protein - FGF1, which could be used in the treatment of difficult to heal wounds, ischaemic disease or diabetes. In the future, this protein may be a carrier of drugs to cancer cells.

Researchers from the Department of Protein Engineering of the Faculty of Biotechnology, University of Wrocław, study the mechanisms of action of proteins - the most important macromolecules in the human body. They also modify proteins with genetic engineering methods so that they can be used for therapeutic purposes.

One of the objects of their research is the human protein FGF1 - a growth factor affecting many types of cells and, among other things, leading to their division.

"FGF1 accelerates wound healing and bone healing, it also participates in the formation of new blood vessels and lowers blood glucose; it can be used as a drug carrier to cancer cells" - says Dr. Małgorzata Zakrzewska from the Department of Protein Engineering, University of Wrocław.

FGF1 is produced in many types of tissues, including smooth muscle cells and epithelial cells, liver cells, epidermis, connective tissue, macrophages and nerve cells. It stimulates DNA synthesis and cell multiplication.

Due to the activation of receptors on the surface of the cells as well as its intracellular activity, FGF1 promotes cell survival, protects them from adverse conditions and counteracts programmed cell death (apoptosis).

By analysing the protein sequence and its structure, scientists design mutations and modifications that will improve or change the properties of this molecule.

"By using recombinant DNA technology, we are able to efficiently produce this human protein in bacterial cells. The DNA sequence of the human protein is cloned into a special genetic construct that is then introduced into Escherichia coli. This way, we get large amounts of protein in laboratory conditions, which we then carefully clean" - describes Dr. Zakrzewska.

Researchers check the properties of a pure protein and analyse whether it has the correct structure and whether it binds correctly to receptors on the cell surface. In their research, they use human cells that they grow in laboratory conditions.

"We check how the protein variants we study affect cell division, multiplication and migration of both healthy and diseased, cancerous tissues. We also verify where the FGF1 protein is located in cells, how efficiently it penetrates the cell and what processes it activates" - explains the researcher.

According to the researchers, due to its properties and regenerative potential, the FGF1 protein is considered a potential therapeutic agent that could be widely used in the treatment of many diseases.

Because this protein is involved in the process of tissue healing and repair, it can be useful in the treatment of chronic wounds, difficult to heal fractures or nerve damage. It also provides a protective effect in the case of cells exposed to gamma radiation. It has angiogenic properties that - according to the researchers - can be used in the treatment of cardiovascular diseases.

Wrocław scientists are also investigating recently discovered properties of FGF1. These properties are associated with cell death prevention and antidiabetic action.

In addition, according to Dr. Zakrzewska, increased expression of FGF receptors in various types of cancer, including breast, bladder, prostate or lung cancer, means that that after appropriate modification this protein can also act as an agent directing the selected drug to cancer cells.

"We`re modifying FGF1 so that it can be used as an effective drug in the future. We construct variants that work longer and are less prone to degradation. We obtain a protein that could be used in the treatment of difficult to heal wounds, ischaemic diseases, tissue damage or diabetes. It could also be used as a carrier of cytostatic drugs to cancer cells" - says Dr. Małgorzata Zakrzewska.

PAP - Science in Poland, Kamil Szubański

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