Metabolomics for dummies
The rapid development of the direction dealing with the study of complex interactions is transforming biology and biomedical research.
A whole line of powerful analytical methods, known as "-omics", leads us away from simplistic approaches to a more systematic understanding of the problems of biology and medicine.
Until recently, technical capabilities allowed scientists to study only a small part of the components of biological systems. "-omics" (including genomics, proteomics, metabolomics), on the contrary, provide an opportunity to look at a more detailed picture in order to define a biological system.
One of these methods, metabolomics, is designed to determine the chemical profile of cellular metabolism in unprecedented resolution. Knowledge of this profile provides a deep insight into the dynamic processes occurring in any biological samples.
Every process that takes place in the cells of living organisms requires energy. This energy is released from nutrients and is spent on the synthesis of new ones, mechanical work, thermoregulation processes, etc. in metabolic processes. Biochemistry often involves deciphering the metabolic pathways through which nutrients and energy move in the cells of the body.
Traditionally, such an analysis was carried out by measuring the activity of individual enzymes or the levels of individual chemical compounds (metabolites) in a biological sample. This approach has provided a number of the most serious achievements in biology, however, it requires a very large amount of time and has its limitations.
Metabolomics, on the contrary, allows us to simultaneously measure the levels of hundreds or thousands of chemical compounds, which provides a much more detailed picture of metabolism. This potential and versatility open up a wide range of possible applications for metabolomics.
How does it work?
Metabolomics has become a reality thanks to two technological techniques. First, a complex mixture of small chemical compounds (metabolites) is released from a sample of cells, tissue, food, urine, an extract of microorganisms or anything else. The next step, known as chromatography, separates the mixture into simpler components.
Each metabolite in the mixture consists of a unique combination of chemical elements that provide its characteristic molecular weight.
After that, an incredibly sensitive device known as a mass spectrometer is used to identify these compounds and change their activity. Modern mass spectrometers allow measuring the mass of very small amounts of metabolites with an accuracy of the mass of one hydrogen atom.
You can imagine how accurate this is with the help of an interactive biological scale developed at the University of Utah. Towards the end of the scale, you can find the metabolites glucose and methionine, and at the very end of it, a carbon atom.
Recently, metabolomics has been widely used in various fields of research. This increase in popularity is due to an increase in the sensitivity and speed of mass spectrometric analysis.
No less important are serious advances in data processing and analysis tools needed to analyze huge amounts of data received. The emergence of a specialized field, called bioinformatics, allows us not to limit ourselves to a reasonable assumption when processing the results. Innovations in the field of computing contribute to the integration of "-omics", mathematics, statistics, systems theory and biology. Bioinformatics has really expanded our capabilities in understanding what happens inside the cell, including how genes and their products are translated into a functional effect.
Why such a fuss?
In medicine, metabolomics is used to identify new diagnostic markers of diseases such as cancer and diabetes. At the same time, we are learning exciting new details about the development and progress of diseases, the mechanisms of action of drugs, as well as identifying new targets for potential therapies.
For example, in this study, metabolomics was used to analyze urine to determine the various stages of prostate cancer. The researchers measured the amount of 1,125 metabolites in 262 clinical samples. These figures give an idea of the level of detail provided.
In our laboratory at the Kinghorn Cancer Center, we combine metabolomics with genomics (mapping of gene mutations) as part of the so-called "head-on solution method" used to better understand the mechanisms of pancreatic cancer. For this severe, often incurable disease, there are very few treatment options.
We have established that pancreatic tumors reprogram their metabolism in such a way as to enable rapid cell division and growth. Our data obtained with the help of metabolomics indicate that these mechanisms are a kind of "Achilles heel" of tumor cells, which we hope to use to develop new treatments.
Metabolomics can also help to understand the effects of the environment, pesticides and pollutants. For example, under the influence of hormonal contraceptives and anti-inflammatory drugs contained in sewage, males of some fish species can transform into females and even spawn.
Metabolomics is also used for quality control in food production. It even allows you to determine how the nutrient content changes during the production of food, for example, the processing of grits (an intermediate product of grinding grain) into pasta from unseeded or refined flour. There are also huge hopes for the use of metabolomics to detect the illegal use of hormones and other drugs in cattle breeding and as doping for athletes.
One of the most intriguing applications of metabolomics is the study of the complex nature of the species. Huge efforts are being made to understand the interaction of soil, climate, yeast and bacteria in fermentation. Even the oak from which wine barrels are made has a certain effect on the chemical compounds that make up the grape juice, which gives the wine its characteristic color and aroma.
In real life – today and tomorrow
In the study of diseases, the detected changes in metabolism form the basis of new ideas about which molecular processes can be influenced by drugs. They can also be used to identify new methods of identifying or classifying diseases into more specific subgroups.
Such discoveries have such far-reaching consequences as the emergence of new targets for cancer treatment, diagnostic methods for diabetes, cheese with better taste qualities, more reproducible batches of beer, more resistant varieties of agricultural plants, diagnostic tests for detecting diseases or aging that cause muscle atrophy, and much more.
Another area in which this technology can play an important role is the detection of pollutants in food (to confirm claims about the organicity of products or the absence of hormones in them), as well as the use of prohibited additives in the cultivation of livestock or the training of athletes.
The advantages of metabolomics, consisting in the possibility of detecting not only the drug molecules directly, but also the products of its metabolism in various body fluids, give hope for the possibility of more accurate screening.
Metabolomics helps us understand how biological function is interconnected with changes in the genome. This approach, when combining efforts with other "omics" to search for relationships between genetic variations and visible manifestations, opens up a more detailed picture for us.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The Conversation (D.Saunders, R-A.Hardie:
"Metabolomics: wine and cheese, curing disease … no doping please").
12.11.2013