On this episode of Translating Proteomics, hosts Parag Mallick and Andreas Huhmer discuss the many ways proteomics can impact our interactions with food. Some of the topics they touch upon in this wide-ranging conversation include:

·      Proteomics and food quality

·      Proteomics and food safety

·      Developing new kinds of food with proteomics

Chapters

00:00 – 01:23 – Introduction

01:23 – 03:27 – Proteomics and alcohol fermentation

03:27 – 05:24 – Food properties and their relationship with molecular composition

05:24 – 07: 42 – How can we use proteoforms to improve food quality?

07:42 – 11:49 – Proteomics to aid plant and animal breeding

11:49 – 14:35 – Proteomics, Food Safety, and Food Security

14:35 – 17:05 – Proteomics and food authenticity

17:05 – 20:36 – Proteomics and terroir

20:36 – 22:48 – Proteomics, the microbiome, and health

22:48 – 24:29 – A fun party trick

24:29 – 30:24 – Creating new foods and flavors

30:24 – 34:33 – Designing food for space

34:33 – End – Outro

Resources

The post-translational modification landscape of commercial beers (Kerr et al. 2021)

·      Paper looking at the ways post-translational modification differ between different beers and how protein content relates to the properties of foam

Heat shock and structural proteins associated with meat tenderness in Nellore beef cattle, a Bos indicus breed (Carvalho et al. 2024)

·      Paper looking at the relationship between proteins and meat tenderness

Comprehensive proteome analysis of bread dicphering the allergenic potential of bread wheat, spelt and rye (Zimmermann et al. 2021)

·      Research measuring the levels of allergens in different kinds of bread

Differential proteomic analysis by SWATH-MS unravels the most dominant mechanisms underlying yeast adaptation to non-optimal temperatures under anaerobic conditions

·      Study using proteomics to reveal how yeast adapt to growth at different temperatures

Foreign.

Proteomics hosts, Parag Malik and Andreas Humer of Nautilus Biotechnology discuss the many ways proteomics can impact our interactions with food.

Some of the topics they touch upon in this wide ranging conversation, proteomics and food quality, proteomics and food safety, and developing new kinds of food with proteomics.

Now let's dive into the conversation with your hosts, Parag Malik and Andreas Huma.

Welcome back, everyone.

I hope you're hungry, because on this episode of Translating Proteomics, we're going to be talking about something that touches all of our lives.

Food.

On a previous episode, we briefly touched on proteomics and food as part of our discussion of how proteomics had many exciting applications.

And most listeners told us that they wanted to know more.

So today we're going to dive into a couple different topics.

We're going to talk about how proteomics can change food production.

We'll talk about how proteomics may be able to make food safer.

And we're also going to talk about how proteomics may help us learn more about how food impacts our body and in general, the relationship between food and health.

Andreas, on our last episode, you talked about how you were working with researchers to identify a cheese protein that had an impact on cheese quality.

Did you have any other personal experiences with proteomics in food?

Absolutely, yeah.

We actually investigated the impact of proteomics in yeast and brewing beer, for example, or in wine.

And so we actually exposed a number of these yeast strains, you know, to different fruit.

And then we, you know, during the fermentation process, we actually did proteomics on the yeast itself.

And that turned out to be quite interesting because even if you used the same yeast, when you changed the fruit, it actually changed the way that yeast, you know, fermented the fruit.

And it was all about the proteins that made a difference in this, in, in this particular case, obviously those proteins that metabolize the sugars in the fruit.

And so that was very interesting.

And we got a lot of feedback from during the poster session and we even had a conversation where it's like, well, let's just do beeromics from now on because it's so much fun.

It's so interesting.

Clearly, scientists and beer, there's a strong connection there.

When I was in graduate school, the lab across the hall from us was developing a strain of yeast that had a higher alcohol tolerance and so that could brew beer that was stronger, higher percentage alcohol beer.

And they ultimately did look at some of the proteomics and tried to Understand what the chemical pathways were that were driving alcohol tolerance in yeast.

And there's a big conversation going on in my hometown, where beer was brewed, where their biotechnology was actually invented, when, you know, Genentech and in the 80s, when Genentech and all the other companies emerged, or whether it was invented hundreds or thousands of years ago and people figured out how to put yeast into a fruit mix and make some alcoholic drinks.

Wow, that's amazing.

One of my other experiences with proteomics in food was chatting with some of the companies that are working on artificial foods and trying to understand, for instance, when you are making a scrambled egg, what is it about the protein composition of a real egg that drives that heterogeneous.

Very interesting profile of scrambled eggs.

How do you make the taste align is really about lots of additives and trying to get the color right, but the texture and the aeration ultimately is driven by proteins.

Yeah.

Well, maybe a personal anecdote on this.

I think about proteomics when I cook or bake.

And the worst thing is then when you take the egg white and you're trying to make stiff egg white and you figure out it's not.

It's not stiffening up.

Right.

Despite the fact you can add a little bit of salt to denature the proteins quicker, or a little bit lemon juice if they still don't.

Well, you pretty much don't get a very good egg white that fluffs up your dish.

So I can imagine how the protein contents, but also the age of the protein that is in your egg is very important in that case.

Right.

Well, and of course, in molecular gastronomy, there's tremendous research into understanding what it is about the molecular composition that drives the properties of the food.

Hervdis from France is.

Is known for his explorations of how you alter the composition to drive different physical properties of the food as well, making things that never existed before and taking advantage of chemistry to do it.

Absolutely, yeah.

I love hearing about these experiments because it all boils down to proteins and chemistry in the end.

And I wish I could replicate some of that in my kitchen at one point.

Well, let's talk a little bit about how proteomics has been used to.

To think about food, and in particular, food quality.

How might we use proteomics to make better food?

Well, the example I mentioned in the previous episode was all about controlling the consistency of proteins with the natural resource or during the actual processing of it.

And I think there is lots of opportunities because obviously we consume natural products and they have a Different composition of proteins.

And so being able to control that at a reasonable level is probably the way to get these consistent sources of food.

The problem is going to be it's very expensive to do that.

Now I think if you really want to characterize a protein, you're going to use a high end mass spectrometer, but it's just prohibitively expensive.

So there's a big opportunity for more accessible technologies to, you know, basically read out what's the composition of my proteins in that particular source.

And so I think what you're talking about is that one might use proteomics as an assessment tool to say, to evaluate different, different types of food, different meats, for instance, to say, all right, I can mechanically perturb my meat to, to study properties of its tenderness, for instance, but perhaps I can also look at the protein composition and there's something about cytoskeletal degradation that allows me to understand those properties.

Yeah, I mean, the interesting part is if you think about animals growing up outside, I mean, they're exposed to many different to the environment and obviously that will change the way that the meat is essentially later on cooked on your grill.

And so there may be maybe not the need for the average home cook to have a tool like this, but I think for consistency in industrial environment, it might be an interesting aspect to sort of guarantee high quality foods.

And basically it's done in Japan today already.

So Parag, is there maybe an option for proteomics to help in characterizing what specifically can be bred in, let's say, plants or as you mentioned, for particular meat production to guarantee the quality or the properties that you would like to have in the food?

Absolutely.

I think when we think about where proteomics can come in, there are two very different places.

One is what we've talked about as assessment is I'm looking at a food product and I want to know general properties of it.

I want to know if it is good, I want to know if it is stable.

But on the other side, things like evaluating different strains of crops, some of them may have different properties for quality, some of them may have different properties for stability.

So for instance, resistance to bacterial or fungal pathogens and those, those traits are, can be studied both endogenously in their native proteomes by looking for proteins that discriminate amongst strains that have long drought tolerance, require small amounts of water.

It can also be seen in perturbation.

So how does, how does this particular plant or animal change when exposed to variation in heat?

How does it change when exposed to variation in food.

And so I think there are exciting opportunities.

And we've seen research into studying how different strains can impact proteomic properties.

Yeah.

I had actually the chance to talk to a number of researchers at the Department of Industries in Australia, Obviously big agricultural industry there.

And, you know, the typical approach in science was that you use genomic tools to characterize what the genome looked like in a plant, and then you would observe the phenotype.

Right.

And the step between was basically, you know, people were unable to probe for that.

And when they switched and added proteomics tools to really characterize the underlying proteome of the phenotype, they made huge progress in increasing yield and in obviously increasing particular properties.

A good example might be, for example, the amount of gluten in wheat.

So if you think about how bread making has evolved from someone who is baking a bread, it's basically the entire morning to let's bake some bread starting at 6:00.

So we have something in the store at 8:00.

So the trend has been that you increase the amount of gluten in your bread in your wheat, and that increases the amount of gluten in the bread.

And then you just have to add a lot of razors like carbonates or yeast to make the bread rise quickly.

And so this way you can produce nice bread that's fluffy in about two hours instead of six or eight hours.

And so that has all been driven by understanding the proteome in wheat.

And so there was a lot of work going on in this.

There's still a lot of work going on in this regard.

One thing that I always thought was very interesting and related to what you're talking about in terms of studying yeast is studying the proteomes of different materials, beer, wine.

And again, what the properties are driving the head on a beer can be done by altering.

Altering the proteome, not just of the yeast that's producing it, but also looking at the proteome of the beer itself, which I was personally shocked that proteins were a component of some of these foods that I just didn't even associate with being proteinaceous.

So, yeah, the foam on the beer itself is probably a product of the ingredients you put in.

Yeah, interesting.

Yeah.

I personally don't like foam that much, but I can see how beautiful Crown the beer is, Is very appetizing.

Yeah.

One other place where I think we've, in addition to engineering, we talk about the processes of making food.

So you just shared with us a story about how changing the process, shortening the process can be really important.

What about just safety?

What about ensuring that we have food that is minimally allergenic, most tolerant to pathogens.

Is there a role for proteomics there?

Oh, yeah.

I mean, we already mentioned the allergen gluten.

A lot of people have gluten sensitivities and obviously there needs to be some kind of test if you produce gluten free products that you test for gluten.

It turns out that gluten is actually very difficult to analyze by proteomics because there's many repeated motifs of short peptides that are really difficult to analyze by peptide based sequences.

And so, you know, immunoassays are doing the best job at this point in time to sort of characterize how much gluten or is there any gluten in the, in the food?

And so, yeah, it's tremendously important for food safety at this point.

Yeah.

I think one of the areas that I've been really excited about is just looking at how again, food security and as part of ensuring that our food is not only safe, but is safe over an extended period of time.

And so when we look at pathogens that are endogenous within the food, can we use proteomics to identify, oh, this particular batch has been contaminated in this way and see evidence of non typical plant in.

In there.

We've seen studies that have been incredibly sensitive, diving deeply into studying carriers, things that come along with the food.

I think the other side of that is just how can we create resistance, intolerance and so that we create strains that simply can't be infected in these ways.

Yeah, I mean, we trust is another very good example.

Right.

Where you need to measure protein essentially, which is a fungi that affects the wheat and it has tremendous effect on your yield.

Or some of these fungi essentially create endotoxins that are dangerous for humans.

And so they actually have to be tested for, particularly if it's a rainy year.

Wheat is typically tested for these endotoxins.

Wow.

And so these endotoxins are they proteins themselves or they're produced by pathogens?

And they're produced by pathogens.

Some of them are short peptides.

Yes.

Wow.

Yeah.

The other part that I would think is also important and when we think about food and proteomics is just authenticity.

So you can go to a food market, let's say in France or Spain, and buy fish and they would have a label that says it's, it's Flander or whatever.

Right.

It's Philadelphia So you don't really know what, you know, what kind of fish it was.

But there's strong regulations now that, you know, control what kind of fish are you, you know, are you allowed to sell fish in the first place?

Obviously.

And so it has been a challenge to actually bring food to the market that is authentic in what it actually is.

So, you know, part of the overfishing problem is that people fish and then declare it to be a different fish that's not being protected.

So there's proteomics examples where you can use a heat shock protein that stays stable and you can just introduce them into a mass spectrometer or even a type of immunoassay and say, hey, by the way, this is a particular protein formed.

It's only in this particular type of flounder and not in a different type of fish.

And so in food authenticity, this has been.

Proteins have been really critical in identifying what kind of fish are actually being offered in supermarkets.

That is an amazing story about.

I hadn't realized there was just so much detail in being able to understand the origins of a flounder or some other fish.

Is this sort of food forensics used in anywhere else?

I know it's being used in European Union where they have strict fishing regulations.

I'm not aware that, you know, this is being particularly applied in this country.

But certainly if you trying to import a fish and claim it's haddock, but in the end it's not right.

There's some test can be applied in this particular case to say, yeah, this can be labeled as this particular fish.

Well, that's amazing.

I'd love to see this also applied to different varietals of maraschino cherries and say this is in fact from this origin, from this location.

I totally agree.

Yes.

Particularly if you pay an extra price to have some particular food that is known to have particular properties.

Absolutely.

We've talked a bit about how different verifying the authenticity of food.

One thing that I've always wondered about is how much is food impacted by or beverages impacted by where they're grown.

Champagne specifically comes from a region in France.

But if we were to take those exact same grapes and grow them somewhere else, would they taste the same?

Would their proteomes change?

Can we use proteomics to understand terroir of different, different types of foods and beverages?

Good question.

I actually don't know.

I think that it's an interplay between the proteins involved, a part of the plant, when the plant grows and produces the fruit or Whatever it is that we're looking forward in the food, But I think it's also metabolites.

And so obviously, if proteins have a different.

There's a different set of proteins that then later on is being metabolized, for example, in the winemaking.

Right.

There would definitely be a difference in the composition of the wine.

So I think it's the consistency of bringing the same plant into the food processing.

But this feels like an opportunity.

This feels like a place where we could imagine taking grapes from one region, moving it to another region, trying to ask the question about just how different is the grape, Just how different is the vine itself?

The plant, has it changed its proteomic properties, and that's driving subtle differences in the grape that we're then experiencing years later getting experiment.

I think it's too expensive right now to do it.

And I think once tools emerge that are much more accessible and cheaper, I think people will do these sort of experiments for sure.

Yes, because it could be that, yes, even if we took the dirt and we took the plant and we moved it to a different location, that there were just so many other factors.

The fact that it was grown on the upper side of the hill instead of the lower side of the hill, which subtly changed the way that the plant responded to sun, that.

That could materially impact the grapes and change the flavor.

And this is an area that has been hypothesized, but I just.

I haven't seen.

Seen research yet on that.

A lot of work has been done in the metabolomic space on that.

But I think, you know, the proteomic space might be actually a much more fruitful ground to do that, because.

Yeah, because you could understand the mechanism.

You could say, where did this come from?

It was this particular pathway that was overexpressed in response to growing on the upper side of the hill.

And then, of course, you could start engineering, you know, different grape varieties that essentially, you know, proliferate that process.

And we see this with dairy products as well, that cattle grazed in different locations are meant to have slightly different flavors of cheese that result.

And you see this very directly in egg products as well, that eggs from chickens grown in slightly different regions, even though they're exactly the same in terms of their species, they look different, they have different textures, they taste different.

And I'd love to dive into what are the proteomes of those chickens and how they led to a completely seemingly different product.

I agree with you.

And then, hopefully, I never have an egg that's already too old to be Used for like making nice macarons.

So let me ask you, we talked about the fun side of proteomics and how proteomics affects the food making the food processing, the sources of proteins in the food.

What about the aspect of health?

How does proteomics maybe shine a new light on proteins and human health?

I think one of the most interesting sets of research that I've seen has been associated with the microbiome and seeing how different proteins introduced into the microbiome affect the bacterial composition, which can then lead to things like changing response to cancer therapy.

And so that link that you can see both in the endogenous composition as it goes in as a prebiotic and ultimately the phenotypic consequence of how does a person respond to this cancer therapy?

How does their immune system, how is it altered and modulated?

I think the proteomics data has been very clear in showing those changes in immune activation throughout physiologic systems and helping connect things that are very far away.

Things like did I eat a pro inflammatory or anti inflammatory diet in terms of a ketogenic diet and the link to cancer effectiveness.

We've also seen that, that there was initially an observational analysis that said there exists this relationship, but then going further to say this actually affects this particular pathway, that pathway is then changed and we see these alterations in the circulating proteome.

So do you imagine that in the future there has been some kind of research done and instead of label saying it contains maybe not particular, it's free of particular allergens, it basically says it will help you with like probiotic today are right, that will help you with this particular aspect of your microbiome or digestion.

Do you think that's going to be part of the equation here?

I could easily imagine that not in the near future, not in two years or five years, but maybe in 10 years we do get some personalization.

So maybe we can leave our audience with a little party trick.

There's glycoprotein that's involved in changing your T spots and it originates from a berry, miraculin.

You can buy them online.

And the party trick is that you put those, you know, this fruit in your mouth and let it rest for about 30 minutes on your tongue.

And what happens is that the glycoprotein essentially covers the sweet receptor on your tongue.

And then if you happen to, or if you add lemon juice or something sour, that actually enables the receptor changes and enables the glyco portion of the miraculin protein to actually occupy the sweet receptor and so despite the fact that you eaten lemon juice or had lemon juice in your mouth, your tongue will send a signal to the brain that says this is sweet food.

So it's a lot of fun, people should try it out.

And you know, it's obviously something that, you know, we could potentially utilize for new types of foods.

Right?

Well, what's amazing about that process is inside the, there's a glycoprotein binding to taste receptors.

It's a ph dependent change.

And so that's why lemon juice activates it is because it actually changes the conformation and leads to this binding.

And so we did this at home.

And strawberries tasted like cotton candy, lemonade tasted like, or lemons tasted like lemonade.

Pickles tasted sweet, which was really strange.

And it's, it's an amazing interplay between proteins and our body.

And it makes you think about what else if we were to just imagine what other crazy things could proteomics enable?

Could it enable us to create entirely new foods that don't even exist today?

Potentially.

I mean, we are experimenting in that sense, right.

With GMO food where we are trying to put particular properties into the proteins that, you know, make the plant resistant to insecticides or insects themselves.

Right.

So we're already experimenting with food in general.

But it's an intriguing idea to think about just changing the protein or making an artificial protein.

What do you have in mind in that regard is that.

Well, I think one of the places where we, we tend to focus is on changing, changing our food supply and our food chain.

But it seems like we could actually create entirely new flavors and textures and that the protein composition, the glycosylation state of different proteins could make for things that are rigid, extremely flavorful and nutritious.

There for instance, was the golden wheat that was very popular a few years ago where you increased the vitamin content and protein content.

Golden rice as well, that enabled and much more nutritious food supply, but it was still rice.

And so I wonder about the food of the future that you taste it, you put it in your mouth and it starts fireworks or something like that.

So, you know, we talked a lot about the, you know, the influence of the environment of producing interesting proteomes that ultimately give us, you know, let's say very interesting wines or other foods.

I don't think we actually need to have artificial foods in that sense.

I think there's plenty nature offers to us.

So you're anti creating entirely new things.

You just, you want to be satisfied and stuck with the foods that we have already.

Maybe we're not stuck, but I think we have plenty of variety of food available to us.

I think the other part that might be really difficult, and I'm pretty sure the food industry is all over that.

Right.

Because we have different compositions of, let's say, taste receptors, that for one part of the population, this particular food may be just phenomenal.

For others, it may just be absolutely horrific.

So like people having their reaction to cilantro, for instance.

Exactly.

So it may be a very difficult task to actually get a food that a lot of people like and it's worthwhile making because a good part of the population just doesn't like it, can't eat it.

So I disagree.

And the reason I disagree is ketchup.

Oh.

So you might have noticed that there's basically one type of ketchup.

You don't see a wide variety of different flavored ketchups.

On the other hand, you see a wide variety of flavored mustards.

And it's because they did studies looking at ketchup and they found that it essentially was perfect, that it was a mix of sweet and salty and sour and umami all together, and that it was nearly impossible to improve on ketchup.

Everybody liked it.

It was the perfect food.

And so I believe that there might exist other perfect foods out there.

We just might need to be creative with how we come up with them.

Well, you're talking to a person who is literally addicted to ketchup.

Maybe I can be convinced that there is engineering that we can do to actually create novel proteins that give us new food experiences.

That's exactly right.

So most of what, when we focus on altering the proteome of, of food sources, we're really talking about very subtle changes.

We're talking about overexpressing something that was already there.

We're talking about finding a combination of a plant amongst a thousand different varietals.

Where we've gotten uncomfortable is introducing either proteins from one species into another or entirely.

We have an entire new wave of synthetic novel proteins that never existed in nature.

And introducing those into the food supply is a little scary.

Yeah, it probably is a safety issue in the first place.

But on the other hand, drugs are completely novel molecules, particularly antibody drugs based drugs.

And so clearly nobody has ever grown an extra arm because they have taken a drug.

Right.

Well, I think this area of nutraceuticals is a hugely emerging area.

And what we haven't really taken advantage of is the proteome and the development of those nutraceuticals.

Now I would argue that we've been doing GMO foods for thousands of years.

If we look at the almond, for instance, the almond several thousand years ago was incredibly poisonous.

But we selected for a varietal that is not toxic today.

And so could we just do that process more efficiently?

Could we pan through hundreds of millions of different varietals, exploring their proteome and at what point, if we're introducing what we're doing through that selection process, would it have just been faster to have taken the toxic portions of the almond out and just synthesized an entirely new almond?

Yeah, you're making a good point.

I'm still very skeptical because a good portion of the experience with food is that it's the variety of different things in the food that essentially creates the long lasting palate, the surprises that you have experiencing food.

So I'll still need to be convinced that completely inventing new foods or proteins that actually supplement maybe our food are direct, the right direction to go.

So I'll keep trying.

So we've talked about different aspects of food security, how to, how to, how to grow it, how to change flavors, how to affect health.

What about foods that we need to.

Let's think forward a couple hundred years and perhaps we're headed beyond Mars at that point.

Or we have just such dramatic changes on our own planet that places that are accustomed to growing particular types of food are no longer able to.

How do we take advantage of the proteome to help us move towards a world where we need to invent entirely new crops or we need to move crops from their current habitats to entirely different ones, like space stations.

Intriguing idea.

How do you create food for a six month trip to Mars, right.

Without having to rely on dried food or any of these preserved food.

But maybe having them produce right on the spaceship, for example, right.

In Star wars we always see these synthesizers where they just press a button and food magically appears.

But assuming that we're not going to have that, we are going to have.

To produce food, it's gonna be a formidable challenge.

Besides the taste aspect, what we already discussed, making sure that you have all the nutrient and the elements of nutrition that ultimately sustain you.

Right.

And obviously it goes way beyond proteins.

But you certainly, if you want something more, a better experience, such as an infusion going into your body, you want to actually have an experience of tasting something three times a as you're in a spaceship for six months.

It's a big challenge.

So you know, I guess to me part of what it comes down to and NASA's doing experiments into this already is how are plants altered by microgravity, for instance?

So we, for instance, seeds and just how they grow, they are looking for gravity to orient themselves upwards and downwards.

And they have sugar filled sacs that fall to the bottom and activate the cell to say, hey, cell this way's up.

And that allows seeds to even turn.

And you can see those changes in the proteome.

So beyond orientation, microgravity likely changes signaling in other ways as well.

And so proteomics to understand the impacts of microgravity or other environmental changes, I think is a founding condition in order for us to explore how we might prepare for growing foods in context that they're not.

Yeah, alternatively, you just do what we do today, right?

I mean, you can buy seeds and you can put them in a little, you know, container and then, you know, create little microgreens in your kitchen.

So, you know, if you don't expect a full, full blown plant develop, right.

You can just eat the, the seeds and they're usually very nutritious and very, very rich.

I think the bigger challenge there is, as you mentioned, is maybe if we have to, on Earth, on planet Earth, not just going to Mars, but on planet Earth, have to find new ways to secure food supply in the first place for a lot of people because some of the areas are basically not useful for production of food.

What do you think happens in that direction?

Well, I think we have to understand sensitivity.

So if you were, how many of these places are food producers for historical reasons, and we haven't necessarily mapped out, how might this particular strain of X grow?

If we were to move it to a completely different place, what would we have to do to change it?

How would its molecular pathways be impacted by these changes?

So I think the first step is just understanding for the varietals that we have, how sensitive are they and downstream from what we see of them wilting or not growing or growing slower, what are the molecular causation driving that phenotypic behavior?

So we should definitely dive into this in a much more detail.

It gets a great topic to discuss in a future episode.

We have had a great conversation covering a ton of interesting topics, talking about the incredible potential that proteomics has to help us improve our food quality, the ways that proteomics can improve both food production and our ability to understand the security and safety of our food, as well as ways that proteomics can produce potentially healthier and new foods that haven't even existed today.

We'd love to hear your thoughts how can proteomics impact the food chain and impact the future of food?

Thanks so much for joining us.

We hope you enjoyed the Translating Proteomics podcast brought to you by Nautilus Biotechnology.

To contact us or for further information, please email Translating Proteomics at Nautilus Bio.