Metabolic Phenotyping in Health and Disease

Biochemist Ian Wilson on the interaction between genotype and phenotype, prediction of metabolic disease, and the analysis of the metabolites

videos | June 28, 2018

Probably, everyone these days should know what the genotype is. It’s the collection of genes that you have in your body. The great thing about genotype is that it’s actually a set of possibilities and potentials. I joke when I say this: “I should be 6 feet tall, with an IQ of 150, but because of my gene interactions with the environment I’m actually five foot eight and have an IQ that’s much lower than that”. So, my genes say that I should be tall and intelligent, what actually happened the phenotype that I’ve acquired is less tall and less intelligent than the potential. One of the things we know about the genes that you have in your bodies is that you were born with them, you got them from your parents and you will die with them largely unchanged. But when you were born, you’re small and helpless, and with time you know that the baby phenotype changed into a young person phenotype, changing the adult phenotype will change into an old person phenotype, but it’s all with the same genes

The phenotype that you have is your body and its shape. Your body is built of cells, that’s proteins, lipids, and metabolites.

Associate Prof. Konstantin Khrapko of Harvard University on mutations in non-nuclear DNA, substantia nigra, and aging of Drosophila's intestine
In the 21st century, we are equipped with a whole array of amazing analytical instruments. We can investigate what’s going on in biological fluids in huge detail. We can do that for individuals so we can do what we call metabotyping – looking at the metabolic profiles of urine, which is a history of what’s going on in your body for the last couple of hours. We can take blood and plasma, and that’s what’s going on in your body right now. Because your blood is in communication with all the tissues in your body. We can also take tissue biopsies if we need to know what’s going on in particular tissue. So in surgery, for example, a clinician might want to know whether he’s looking at a cancer cell or not. Some of the metabolites will tell you that, as well this gives us a very detailed picture of what’s going on.

On the basis of a huge database that we have about lots of other people, who had that condition, we would hope to be able to make a prediction as to which drug treatments you should get, and what your metabolic trajectory through your treatment should be. That’s the power of metabolites because they’re dynamic, they change with time very quickly, weareth genes – you’re stuck with them.

Professor, Faculty of Medicine, Department of Surgery & Cancer, Imperial College London; Chair in Drug Metabolism and Molecular Toxicology, Imperial College London
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