Why is proteomics better than genomics



The Proteomics (English: proteomics) comprises the research of the proteome, i.e. the entirety of all proteins present in a cell or a living being under defined conditions and at a defined point in time. In contrast to the (rather) static genome, the proteome is (highly) dynamic and can therefore change in its qualitative and quantitative protein composition due to changed conditions (environmental factors, temperature, gene expression, drug administration, etc.). The dynamics of the proteome can be visualized in the following example. A caterpillar and the butterfly that emerges from it contain the same genome, but still differ externally due to a different proteome. The same is true for a tadpole and the frog that emerges from it. The changes in the proteome can sometimes take place very quickly, for example through phosphorylation and dephosphorylation of proteins, which play a very important role in signal transduction.

definition

Essential sub-areas are the elucidation of protein-protein interactions, which mainly depend on the tertiary structures of the proteins and the interactions between their domains. The quantitative analysis of protein expression also belongs to the field of proteomics. It thus supplements the data obtained in the gene expression analysis and provides information about the components of metabolic pathways and molecular control loops.

The key techniques of proteomics thus support the elucidation of the 3-D structure of the proteins and the individual protein identification in protein mixtures:

Role of proteins

We call the protein inventory of a cell a proteome. Proteomics tries to catalog all proteins in the organism. The blueprints for proteins can be found in the genetic make-up. Thus, proteomics is primarily concerned with the results of sequenced genomes. If the genetic material DNA only stores information, the protein molecules made up of amino acids fulfill many tasks. They are the basic substance of life and act as antibodies to ward off diseases, act as enzymes to enable digestion and act as muscles to ensure movement.

In contrast to the stable genetic makeup, the protein balance of a body is constantly changing. The caterpillar, pupa and butterfly carry the same genes in their cells, but the composition and interaction of their proteins differ significantly. Proteins are therefore the cause of the diversity of life.

aims

medicine

Medicine hopes to find new active ingredients against cancer, infections and certain nervous diseases. Ailments such as sickle cell anemia, Alzheimer's disease or Creutzfeldt-Jakob disease are based on incorrectly formed proteins. If it is known which protein is responsible for a malfunction, it is possible to specifically develop a small molecule that docks on this protein and switches it off. Antiviral drugs for AIDS and flu are based on active ingredients that were created in this way.

Industry

More powerful detergent enzymes and pesticides are also conceivable.

biology

Biologists hope to find out how life works. The biophysicists are already raving about a "molecular anatomy"

Problems and new trends

After some sobering experiences with genetic methods such as microarray analysis, some scientists are also somewhat skeptical about proteome research. Friedrich Lottspeich from the Max Planck Institute (MPI) for Biochemistry in Martinsried near Munich warns of exaggerated hopes: "For the human sector, research is currently still too complex anyway [..] But for an analysis of yeast, which is a good model system of course nobody wants to spend any money again. " Lottspeich is President of the German Society for Proteome Research (DGPF).

The biophysicist Klaus Gerwert, coordinator of the Protein Center at the University of Bochum, also sees a long way to go: "Proteomics alone is like collecting and cataloging flowers - you don't yet learn from them how nature works." So far there is a lack of concepts for understanding the still unmanageable database to be expected.

The complexity results from the many possibilities: According to Friedrich Lottspeich, humans have an estimated several hundred thousand to millions of proteins. A single gene produces an average of five to ten proteins, in some cases several hundred. To fully grasp this complexity is a challenge that current methods are not yet able to cope with. On the other hand, proteome research is developing rapidly. This is due in particular to a constant improvement in mass spectrometers, which are becoming more and more precise, sensitive and faster.

Another important step is the development of quantitative methods such as the SILAC or ICAT method based on the use of stable isotopes or the MeCAT metal coding, in which metals of different weights are used to mark proteins and peptides from different protein samples. The latter allows the proteome-wide use of ultrasensitive elemental mass spectrometry (ICP-MS) (detection limit in the ppt to lower ppq range) for the first time in the multiplex approach, which allows a higher sensitivity of over 2-5 orders of magnitude in protein quantification and a linear dynamic measuring range of at least 6-8 orders of magnitude having. MeCAT In contrast to the other methods, which “only” quantify relatively at the peptide level, advantageously a relative and even absolute quantification at the protein level, which makes protein species such as post-translationally modified proteins more accessible for quantification. The ICP-MS is calibrated with protein / peptideU.Ndependent metal standards; the need for a protein-specific synthesis of standard peptides is thus eliminated.

The classic proteome analysis only examines whether a certain protein is present (or detectable) or not. Quantitative methods, on the other hand, allow statements to be made about the amount of the individual proteins. In this way, it can be examined, for example, whether certain proteins are more common in cancer cells than in healthy cells.

If you combine quantitative proteome analysis with other biological methods, you can also make statements about the function of proteins (e.g. protein-protein interaction). Modern proteome research therefore goes far beyond the mere cataloging of proteins.

Research focus HUPO

Similar to the genome organization HUGO, the researchers at the International Human Proteome Organization HUPO share the work that arises worldwide. Germany focuses on research into brain proteins.

Systems biology

Systems biology is a new research area that builds on proteomics. This no longer tries to look at the individual parts of a cell alone, but tries to describe the interaction of all individual parts within a system and its environment. In addition to proteomics, this also requires mathematical models that make up the system in silico simulate.

Trivia

The name "proteomics" comes from three scientists from Sydney. They were of the opinion that it was not very easy to get money with the scientifically correct names and so the term "proteomics" was born in a beer whim.

See also

  • -omics
  • Bioinformatics
  • Human Proteome Project

literature

  • Hubert Rehm: The experimenter: protein biochemistry / proteomics. 4th edition. Spectrum Academic Publishing House, Heidelberg 2002, ISBN 3-82-741195-5