Tomatoes, Resveratrol and Humans

Hi everyone,

Since starting up on instagram I have had quite a few questions about my project- and about why I am working with human cells when I am a plant biologist! So, in this weeks post I am going to talk to you a bit more about my PhD research.

In one sentence: my project is looking into the medical applications of the plant compound resveratrol and its derivitive pterostilbene. My project is split into two halves: the plant half, and the human biology half.

So this post doesn’t become too long- this week will focus on the plant half of my project, and the compound I work on- Resveratrol. I will delve into what I do in my project a bit more later, but first IĀ  want to share some history, and controversy surrounding resveratrol…

Background and some controversy

In the late 1990s some scientists were looking at the relationship between coronary heart disease, and dietary cholestrol intake across European countries. As expected the countries which had a higher dietary intake of cholestrol also had a higher death rate due to coronary heart disease. However, France was different. Despite the high amount cholestrol consumed by the french, the death rate due to coronary heart disease was at a similar level to countries which consumed much less cholestrol. This led to the development of the so called “French Paradox“.french paradox.jpg

So, what was going on in the French diet?

Scientists decided to look into the french diet in more detail to try and work out what it was that the french were consuming that could seemingly counteract the negative affect of their high cholestrol diet.

lab cartoonAfter numerous experiments, and studying of data, scientists decided it was the consumption of wine. Red wine to be exact.

But surely, it couldn’t be the wine..? Maybe it was something in the wine?

Some more experiments were carried out- on the red wine- which was found to contain high levels of the the compound Resveratrol. res

Identification of Resveratrol in red wine sparked a massive surge in research into this compound. Since its initial discovery resveratrol has been found to have a whole range of health benefits ranging from anti-inflammatory affects to tumour-supressive qualities and anti-oxidant properties.

The “french paradox” has now been proven to be incorrect, and unfortunately, consumption of red wine probably won’t help you stave away the affects of a high fat diet. As for red wine and resveratrol- well, resveratrol is in red wine, that is true. But probably not in a high enough quantity to be truely beneficial for you.

Unfortunately the “French paradox” has tarnished resveratrol somewhat- it is often one of the only things people know about resveratrol. This teamed with ‘alternative diets’ promoting the consumption of anti-oxidants, does mean that some people look at latest claims about resveratrol with suspicion.

But, despite all of this, the medical applications and properties of resveratrol are worth studying! And, if not for the “French Paradox”- identification and subsequent study of resveratrol may not have happened.

A great scientific review of resveratrol- its potential, and challenges surrounding its used can be found here. In particular, one of the biggest areas of potential for Resveratrol is as a topical skin treatment- which is where my project comes in.(This will be talked about in the next post!)

Ok- But what exactly is Resveratrol?

Resveratrol is a plant stilbene, which is normally produced by plants in the response to fungal or bacterial infections. It is not produced in that many plants- grapes, spruce pine, and japanese knotweed are the major producers of resveratrol, but even in these plants the production levels of resveratrol are not exactly massive.

This is where part one of my project comes in: Using tomatoes as a biofactory to produce resveratrol.

Tomatoes do not naturally produce resveratrol, however they do have the majority of the pathway which leads to the production of it. I like to think of this like a network as in the diagram below. Tomato has most of the beginning pathway components to be able to produce resveratrol- but is missing one enzyme preventing the production of resveratrol.

By inserting this missing enzyme we can produce resveratrol in tomato.

20180216_143449(1)
To get the yellow product, the blue circle needs to be converted to the grey. Without this conversion the yellow product can’t be made.

In fact, my lab did this before I came.

However, resveratrol was produced everywhere in the plant- in all the tissues- and this caused some adverse affects to the plant. Mainly the plants didn’t grow well, and were also sterile- making them less than ideal.

My project therefore looked at developing a new line of tomatoes- ones which produce resveratrol just in the tomato fruits, rather than throughout the plant. In addition, recent progress in the lab had identified a transcription factor which we also wanted to add. A transcription factor acts to boost flow through the resveratrol production pathway, and therefore produce more of the final product- think of it like turning a tap to increase water flow.Ā  So we would get tomatoes with even more resveratrol in them!!

In addition, I made another tomato line which was engineered to futher process resveratrol to pterostilbene. Pterostilbene is resveratrol plus a methyl group- this methyl group may increase the stability of the plant compound, and also give it more potency.

Pterostilbene
The structure of Pterostilbene

So- how can this possibly link to human health?

Well, I am taking the tomato juice itself- containing resveratrol plus a bunch of other health-promoting compounds (such as flavonols which are produced via the same pathway as resveratrol) and looking at what happens to the expression of genes in human cells- specifically skin cells… which I will go into in more detail next time!

 

I hope you have enjoyed this journey into my work- if you have any questions please do ask and I will try my best to answer them šŸ™‚

I am currently studying at the John Innes Centre in Prof Cathie Martins’ Lab , and the University of East Anglia with Dr Jelena Gavrilovic. My work is supported by the BBSRC, and I work as a industrial case student linked with the company: Persephone Bio.

 

Featured image source: Wikimedia

 

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