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Can you explain how metabolomics works?

Can you explain how metabolomics works and what potential it offers for future scientific developments?
Benjamin Warner from Norfolk (Age: 15-24)

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One Response

  1. Hi Benjamin,

    This is lengthy answer but to do the subject justice I think a short answer does not suffice.
    Of courese I could give you the short answer namely that metabolomics is aimed at measuring all metabolites in an organism to determine how the organism functions and how it reacts to endogenous and exogenous stimuli; but I think the story will be clearer if you read the longer text I wrote below. There is namely a close relation between the genes, the proteins and the metabolites in the body. This culminates in an extremely interesting (but very difficult field called systems biology which intends to study an organism as a whole using very advanced software algorithms and supercomputers.)

    Below my longer answer:
    Metabolomics is what we call one of the -omics sciences. The three big sciences in this field are called genomics (thought often this one is called on transcriptomics), proteomics and metabolomics.
    All three methods are very important for studying biological systems. And to be more specific: to study why certain biological systems are different from others. The scientists in this field are helping mankind cure diseases by helping finding new drugs or helping to understand how organisms work!
    A simple example: we know that certain people have genes that predispose them to breast cancer. By doing a DNA test on a persons (often called screening) we can find out if a person indeed has inherited these genes from his/her parents and should therefore remain vigilant to recognize the symptoms of cancer and check regularly to get early diagnosis and treament of cancer to get the best and earliest treatment.
    As you hopefully see, in this way “genomics” can help people to know if they are at risk for a certain disease.

    A note about genomics: often a different approach is used which measures how often the genetic data is copied into mRNA. Although this concept is a bit difficult, you can find enough extra information on the internet.
    Basically it boils down to the fact that the genes in the genetic code are actived due to a certain situation or stimulus occuring in a cell/tissue which results in the transcription of the DNA to “messenger RNA”. This transcription tells a clinician a lot about the disease state of a person.
    For instance if you cut your finger (let’s hope this doesn’t happen too often to you 😉 ) the inflamed tissue will show a reaction to repair the tissue. The response is fundamentally coded in the genome and results in what we call a higher transcription rate of “messenger RNA (mRNA)” for making proteins that repair the tissue damaged by the cut.

    Okay, so far I have explained genomics and that which we call “transcriptomics” e.g. the scientific study of measuring which parts of the genome are copied into mRNA after an event, disease or other event occurs at the cellular/ organism level.
    Genomics and transciptomics are both VERY important in science but also in the clinic where genomics/transcriptomics data are used to help in prognosis (i.e. do you have the propensity to develop a disease), diagnosis (do you actually have the disease) and monitoring disease progression and treatment efficacy (how well is the body responding to a treatment; let’s say chemotherapy).

    Now we can turn to the second part of the “-omics trininity”, genomics/transcriptomics, proteomics and metabolomics, namely proteomics.
    As you may now, DNA is copied to messenger RNA (mRNA) which is delivered to the ribosomes where the ingenious cellular machinery turns the code of the mRNA into proteins (mainly enzymes).

    More info on mRNA: http://en.wikipedia.org/wiki/MRNA

    In turn these enzymes are the incredible biomolecular machines that perform the operations necessary for the body/tissue to regain what we call “homeostatis”. In case of the finger cut this means that the inflamatory response is started (pain, swelling, sensation of hotness of the skin and redness of the skin due to increase perfusion of blood.

    The study of the formed proteins and their function (which is often still not totally understood) is the basis for the important field of proteomics. Here scientist are determining which proteins are formed and what their function is in the cellular processes started at the genomic level. An interesting application of this field is the development of new pharmaceutical drugs that can have an effect on these enzymes and help the enzymes do their work better or block them in case they are aggravating a disease situation (as an example acetaminophen blocks an enzyme called cyclo-oxygenase II which in turn reduces the pain a patient feels due to (chronic) inflammation).

    Re-capping: genes are activated by cellular stimuli which results in messenger RNA which induces ribosomes to make enzymes that are intended to help the human body regain its natural healthy state (this is called homeostatis).

    The final and not less important scientific field in the “trinity” is metabolomics. In this field scientist are determining which compounds are formed due to the enzymes and the metabolism occuring in healthy and ill people. As such metabolomics is different from the other fields discussed because it measures a lot of different compounds and finds the relationships between the concentrations of metabolites and the state of the human body.
    Personally we like to say that metabolomics gives good information about the current status of the biochemical processes in a living being. This is called the phenotype as opposed to the genotype (which is solely related to the genetic information in a living being).

    To give an overview of what we do in metabolomics:
    -we develop methods to determine the metabolites which occur in a certain living organism. Here we aim to find the identity of the metabolite (e.g. is is a sugar or a fatty acid) and the concentration (e.g. is a patient ill because there is a lot of the metabolite or is the patient healthy because the metabolite profile appears to be normal). A very common technique used here is “high-performance liquid chromatography coupled to mass-spectrometry.
    -another aspect of metabolomics is that we are not trying to measure only one metabolite at a time (e.g. cholesterol) but we are measuring a lot of metabolites from one sample and preferably through time. This last aspect allows us to discover if a disease is improving or worsening.
    -to perform the analysis of the often extremely complex data we use computers a lot to perform data-analysis (called biostatistics and bio-informatics)
    -metabolomics is relatively new to science and was preceded by the other -omics sciences (genomics, transcriptomics and proteomics) however a different version of our field existed long before called “metabolic profiling” which is similar to a reasonable degree.

    As a final though experiment to show how important metabolites are I want to show the following:
    A catterpillar which will later become a beautiful butterfly has only one set of genetic code. But during its pupation it changes completely into an animal with totally different properties. So it is clear that the genetic code does NOT tell everything about the actual state of an organism. Therefore it is important to study all three levels of organism organization namely genomics/transcriptomics, proteomics and metabolomics. In a few years time we hope that all these data can be combined and processed so we get a complete overview of how an organism works and responds. The field that works hard at achieving this is called “systems biology” and is very interesting!

    I hope this lengthy answer is useful for you.
    Note that a lot of information is available on the internet to discover more about the exciting fields of genetics, proteomics and metabolomics. So doing some research of your own will likely broaden your insight into the interesting -omics fields

    All the best,
    Heiko

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