Mitochondria, stem cells and Bioinformatics: A new look for heart failure

Dr. Valentina Parra, academic at the Faculty of Chemistry and Pharmacy of the University of Chile, recently awarded a project from the International Centre for Genetic Engineering and Biotechnology (ICGEB), which will allow you to develop a complete line of research, focused on Heart Failure. The project, which lasts for 3 years, begins this 2019, and is expected to include areas such as bioinformatics, cell biology and molecular biology.

Based on the investigation into the behavior of normal stem cells where proteins related to the control of mitochondrial function will be modified, as a reductionist model for the study of heart failure, Valentina Parra, Biochemistry and PhD in Biochemistry of the University of Chile, aims to find new molecular targets that in the future, help in the development of new drugs for this disease , which, among other things, has increased its prevalence in the population in recent years.

"It is common to hear that much of the population has had or knows someone who has had a heart attack. In this context, and while the associated mortality rate is not as high, as many survive, it is the consequences of this that greatly harm the quality of life of thousands of compatriots. In this sense, one of the main problems associated with this disease is that there is no treatment that attacks; and while there are drugs that help shovel symptoms, they don't cure the disease itself," he explains.

Under this prism, dr. Parra's research uses a model of heart failure in human stem cells that will be differentiated to heart cells, which, together with bioinformatics and molecular biology tools, will allow a search for new possible molecular targets to, in the long term, generate effective treatments for such pathology.

Metabolic changes: A common factor

One of the points that contributed to the generation of this line of research was to understand that the different types of heart failure have a point of convergence in their etiology. Although it is known that this disease responds to different origins and, therefore, there are different characteristics, it is metabolic changes, the common denominator for its development and progression. Along this path, researchers have a key protagonist for such alteration at the molecular and physiological level: Mitochondria.

"If we manage mitochondria and manipulate some of its proteins such as DRP1, which regulates the morphology of the organelle - which in turn has already been studied to be altered in heart failure of different types - and generate a network of expression for all messenger RNOs and all the proteins that are being expressed at the time, we could look for what is in common with what is already published around the different types of this disease. This, in turn, would make us able to generate regulatory and transcription networks to test the results we get in our stem cells differentiated to heart cells, as well as in animal models of the disease," she says.

As it is a project that occupies quite a bioinformatics, Dr. Parra and her team, is also collaborating with a professor at O'Higgins State University, who is an expert in transcriptional and bioinformatics regulatory networks, Dr. Mauricio Latorre. On the other hand, the researcher also collaborates with Dr. Fernando Ezquer, of the University of Development, who provides them with healthy human stem cells, in which the protein DRP1 will then be modified, thus modifying the function and mitochondrial metabolism.

"The idea is to develop a well-reductionist model around heart failure, so that it is bioinformatically compared with existing studies, which respond to the different types of pathology. In that sense, one of the things we postulated was that our team, through bioinformatics and molecular tools, is able to handle all the information that is available around the area," he says.

The nomination

Dr. Valentina Parra, who ran for the project in April 2018, and one of the factors that helped her in the positive reception of the writing, was the publication of the paper: "Down Syndrome Critical Region 1 Gene, RCAN 1, Helps maintain a more fused mitochondrial network", in the prestigious magazine Circulation Research.

"With the paper already published, we were able to explain and justify, that with the tools we manage in the laboratory we would be able to lift and carry out a project like this. Finally, the commission loved the project, which allowed us to attach it with a very high score and also very good comments," agrees the PhD in Biochemistry at the University of Chile.

In this context, the funds of the International Centre for Genetic Engineering and Biotechnology (ICGEB), respond to international funding. However, the team is made up of Chilean researchers. The project, which has an initial duration of 3 years, involves the University of Chile (where the project is led), the new State University of O'Higgins and the University of Development.

"We have to start working quickly on this project, since 3 years is not much time. That is why in January we will gather as much information as necessary to proceed with the purchase of the materials that will allow us to start modifying the stem cells, their differentiation and the subsequent extraction of data. Which will then be subjected to bioinformatics analysis," he explains.

Finally, Dr. Parra emphasizes that bioinformatics is an area that will enter this project very strongly. In fact, most of the first year, it will depend on her. "We always think bioinformatics is the best option we have right now, to learn more and more about how to deal with the heart failure problem. This, beyond seeking specific knowledge, because as we know very little, we need to look into the broad, and from the wide, start to reduce. That is why we postulate this project, which uses a broad vision, applied in a reductionist model", concludes biochemistry.

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Journalist: Patricio Grunert Alarcón. ®
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Quote as source a: 4ID-CONGRESS® / Patricio Grunert Alarcón, All rights reserved. ®