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Diffusion

Dimensions of proteins

Researcher develops a kit with plastic parts that shows protein structures in three-dimensional form

One of the consequences of the mapping of human genome and of other similar projects is the increase in the need for studying proteins, organic compounds made up of long chains of amino acids and coded by the genes found in all living beings. They are responsible for various chemical functions in the human body, from digestion to transporting oxygen and reproduction. One of the biggest problems for scientists and students is precisely visualizing how these proteins relate and stick to each other. The difficulty has a simple reason: the chains of amino acids are structured in three dimensions. Looking at a figure in two dimensions in a book and imagining it in space is not a trivial task.

It calls for a lot of training. Thinking of reducing the time taken learning and facilitating the life of those who research into these substances, a British professor who has settled in Brazil, biochemist Richard Garratt, from the São Carlos Physics Institute (IFSC), of the University of São Paulo (USP), decided to create a tangible model, capable of representing proteins in three-dimensional space. The result is a kit of proteins made up of colored pieces of plastic that symbolize the protein structures most common in nature, such as hemoglobin, responsible for transporting oxygen in the blood system, and insulin, which controls the levels of glucose in the blood.

According to Garratt, there is nothing in the world similar to it. That is why, in February this year, he put in a request for a patent in Brazil, with the National Institute of Intellectual Property (INPI). At the moment, he is trying to do the same with the international patent. “As soon as we complete the international patent process, we will be studying a way of producing and selling the kit in Brazil and abroad”, says Garratt. Three forms of marketing it are under study: direct selling, creating a company to produce and sell it, or licensing. “In Brazil, there is still no definition, but abroad I believe the best will be licensing”, the professor observes. For the time being, the kit is not being shown to any company. “We are carrying out a few modifications in the molds, and we cannot yet produce the parts on a large scale.” In a few months, though, the product should be on sale. The price has not been defined, but it should not be expensive.

For Garratt, whatever the way of marketing it is, the intention is to disseminate the use of the kit in universities and secondary schools in Brazil. “We do not want the price to be a barrier to acquiring the material”, he says.The inspiration for creating the material came during the congress of the Brazilian Society for Biochemistry and Molecular Biology (SBBq) in 2001,held in the city of Caxambu (SP). “I was beside the swimming pool at the Hotel Glória, and Professor Glória Franco, from the Federal University of Minas Gerais (UFMG), asked me if it would not be possible to reproduce a kind of model of an atomic structure, which has already been on the market for years, but for a much cheaper price. Garratt recalls. “My reply was that it was possible, but I began to think that it would be much more interesting to do something different. Something that nobody had ever done before and that was not to be found on the market. That was how I got the idea.”

The conversation made him remember the difficulties he had in explaining to his postgraduate students what a protein in three dimensions is like. The concern is not a new one. He had already tried some other artifices. When he began giving lessons at the IFSC 11 years ago, three years after arriving in Brazil, he improvised a few models. “I would buy a few meters of copper wire at hardware stores and would bend it. This means using the hand to put bends along the wire, in such a way that the result represents the path followed by the chain of amino acids in three-dimensional space.

The idea is to show that the compact structure of the molecule is intimately related with its biological activity.” In fact, bending the wires was also an improvement over an older idea that Garratt had seen in Britain. “Bending wire by hand was inspired by my supervisor for a master’s degree, Janet Thornton, now a director of the European Bioinformatics Institute, in the city of Cambridge, in England. She used to bend strips of metal to illustrate how proteins are folded up, except that it was difficult to bend them, besides which it often caused cuts in her fingers”, Garratt remembers.

Design and production
After the SBBq’s meeting, Garratt let the idea settle and decided to sophisticate his model. He presented the project to Professor Leila Beltramini, the coordinator for diffusion at the Center for Structural Molecular Biotechnology (CBME), one of the ten Research, Innovation and Diffusion Centers (Cepids) financed by FAPESP. Leila liked the project, and the pair of them, together with the team from the CBME, began to work on the design of the parts. In eight months, the first prototypes of the molds began to come out of the plastic injection machine at USP’s Center for Popularizing Science and Culture (CDCC) in São Carlos, which is working in partnership with the Cepid on the kit project.

With the first parts, Garratt decided to test the effectiveness of the product in practice. He and other members of the CBME have run workshops at events of the SBBq and the Brazilian Society of Genetics (SBG), setting a challenge for the pupils present (30 to 40, on average): build a protein with the parts from the kit. The results are encouraging. After the 20-minute presentation, most students manage to complete the task in one hour. The test has now been done with over 200 pupils, who also filled out a questionnaire at the end of the challenge. In it, 87% of the people said that the kit is easy to handle, 99% that it is capable of developing reflective thinking, and 97% that it facilitates assimilation of the concepts. The next step is to test the kit in secondary schools, an idea that is part of Garratt’s original project.

The kits, though, may have uses not foreseen by the professor. For example, there are professors wanting to use the kit to help them in their research works. “A professor from Yale University, in the United States, Arthur Horwich, saw the kit and said that he intends to use it to help in visualizing the structure of the amyloid fibrous protein associated with several diseases, such as Alzheimer’s disease,” Garratt says.

In the same period that he created the protein kit, Garratt had another idea, inspired on his observation of a game played by his stepson. “Watching him play supertrump, a pack of cards with different cars, I had the idea of doing the same with amino acids”, he says. The game is one in which each player chooses a characteristic of the vehicle he wants to bet on (its top speed, for example) and puts the card on the table. The one who has the car with the highest speed wins the round.

There are also equivalent packs for aircraft, motorcycles and now one for amino acids, which was given the suggestive name of Aminotrump. For those studying the structure of proteins, it is very important to know the physicochemical characteristics of the amino acids, but it is also very boring to learn them by heart. Aminotrump seeks to make this task more attractive. “Similar ideas formulated by other members of the team may lead to new products in the near future.”

Tripod strengthened
The works done by Garratt, though, would not be possible without the Cepid’s support and funding. “It was very important, because it obliged us to think about what we could contribute towards the diffusion of knowledge.” And he adds: “The great merit of the Cepid in this case is that it involves the tripod research (protein structure), diffusion (a kit used to create a new form of teaching) and innovation (transferring the technology to production).In parallel to Garratt’s work, Leila made a DNA kit. The idea arose independently of the protein kit, at the same time, and with the same objective: to make life easier for students and teachers in the classroom. Leila too did an analysis of the benefits from the use of the kit with teachers and pupils at universities and secondary schools, and the results were similar to those achieved by Garratt. The development of the protein kit, though, has not ended. He is also to create a CD to explain how to use it, and to improve the manual, to facilitate its use amongst secondary school pupils.

The Project
Protein kits; Modality Research, Innovation and Diffusion Centers (Cepids); Coordinator Richard Garratt – Structural Molecular Biology Center (CBME); Investment R$ 80,000.00

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