2013/02/25

The great human protein 'encyclopaedia'

- The Basque research centre CIC bioGUNE is participating in one of the largest international science projects after the Human Genome Project.

- Bodies from all over the world who have joined together to form the Human Proteome Organisation (HUPO) are participating in this project, which aims to identify all proteins expressed in the human body.

- CIC bioGUNE, which already forms part of the HUPO sub-project aimed at discovering the proteins present in the liver, will also take part in the new initiative aimed at cataloguing all representative proteins coded by the genome.

(Bilbao, 25 February 2013).- The Basque bioscience research centre CIC bioGUNE is an active participant in one of the largest collective studies in world science, namely creation of the great 'encyclopaedia' of the proteins in the human body. This ambitious initiative, which forms part of the international Human Proteome Organisation (HUPO) project, is aimed at deciphering the proteins expressed by our bodies. The challenge faced by this project is similar in size to that of the Human Genome Project, which in 2001 deciphered the DNA sequence of humans and found that it consisted of 20,300 genes.

HUPO is an international non-profit organisation created in 2003 in which the majority of European countries, the USA, Canada, China, Australia, New Zealand, Brazil, South Korea, Thailand, Taiwan and Japan participate. Its aim is to publish a map of the human proteome, in other words to identify all proteins in the human body. Subsequent application of this knowledge in the healthcare field is expected to lead to the identification of new diagnostic markers and the development of new therapies, especially considering that the vast majority of current drugs act on proteins.

HUPO is a large-scale international project that was initially proposed as having an organ-based approach, in other words a total of 13 research sub-projects aimed at identifying the proteins present in plasma (HPPP, Plasma Project) and human organs such as the brain (HBPP, Brain Project) or liver (HLPP, Liver Project) were launched. Indeed, the head of the proteomics platform at CIC bioGUNE, Félix Elortza, has been participating in the Spanish consortium involved in the latter project from the outset.

As the work has progressed, it has been found that concentrating the search for human proteins on organs and plasma has several drawbacks as the proteins expressed in the various organs are very similar. As a result, the project has been redefined somewhat, without abandoning the projects cited above, and, as a result, the HUPO platform has created a new major project to search for the proteins coded by genes, known as the Chromosome-Centric Human Proteome Project (C-HPP).

This major international project, which was launched recently, is intended to identify at least one protein coded by each of the 20,300 genes in the human genome. Genes code proteins that play a specific role. As such, the C-HPP project has been divided into 24 working groups, one for each human chromosome. Chromosomes are segments into which DNA is divided and can contain from a few genes (chromosome Y) to as many as 2000 (chromosome 1).

In order to confront the huge scale of this challenge, each of these working groups comprises various research centres from the same country. The chromosomes were shared out between those countries with the greatest experience in the field of proteomics, the discipline that studies the proteins expressed by a cell, tissue or organism.

A special edition of the Journal of Proteome Research in which the results obtained to date by the C-HPP initiative are described has been published recently.

- Chromosome 16

The Spanish working group was assigned the study of the representative proteins for each gene coded by chromosome 16. The aim of the initial phase of this study is to detect those proteins coded by this chromosome that had not been detected previously. To this end, a total of 16 research centres and institutes came together to form ProteoRed-ISCIII, the Spanish proteomics research network. These centres include CIC bioGUNE, with funding from the BBVA Foundation.

Although the majority of diseases cannot be linked to genes from a single chromosome, it is thought that chromosome 16 codes for genes related to cancer, obesity, neurodegenerative diseases, metabolic diseases, etc. It is estimated that at aproximalety one third of the proteins coded by chromosome 16 have never been detected.

The project, which is still in its preliminary phases, is testing new mass spectrometry methods (an ultra-sensitive technique that allows proteins to be detected and quantified) that should allow a very high level of protein detection and quantification to be achieved. This will allow several proteins to be monitored in a single experiment, thus increasing, for example, our ability to discover new molecular mechanisms and providing the possibility to achieve a better diagnosis.

According to Félix Elortza, "this international project has provided ProteoRed-ISCIII with the opportunity to play an active role in the first human proteome map". "Although the map we generate will only be version 1.0, it will nevertheless allow us to place Spanish proteomics laboratories at the forefront of this scientific achievement and will also help to speed up the development of the highly sensitive analytical methods required by a project of this type", states Dr. Elortza.

"Needless to say, this would result in the development of more complex biomedical projects that will help to clarify currently unresolved problems and result in improved diagnosis, prognosis and discoveries in the field of biomedicine", concludes the CIC bioGUNE researcher.

- Proteins

Proteins are a type of biological macromolecule which, together with lipids, nucleic acids (DNA and RNA) and polysaccharides, are the main building blocks of all living things. Proteins are involved in almost all cell processes and are constructed from a sequence of small molecules (amino acids); the order of this sequence is determined by the genes. In a series of biological processes, cells manufacture proteins, which become authentic cell-based tools with multiple roles (structural, mechanical, immune response, etc.). The sequence of proteins is determined by each of the genes revealed by the Human Genome Project.

References for the study

Spanish human proteome project: dissection of chromosome 16

Segura V, Medina-Aunon JA, Guruceaga E, Gharbi SI, González-Tejedo C, Sánchez Del Pino MM, Canals F, Fuentes M, Casal JI, Martínez-Bartolomé S, Elortza F, Mato JM, Arizmendi JM, Abian J, Oliveira E, Gil C, Vivanco F, Blanco F, Albar JP, Corrales FJ.

Journal of Proteome Research 2013 Jan 4;12(1):112-22.