It’s Not Just A Trend

The Critical Need for Celiac Disease Research

Maria Rottersman

FFAR Fellow, UC Davis

Davis, CA

  • Food Systems
  • Production Systems
  • Scientific Workforce

Why Gluten?

My research can be a hot-button issue. But even as public opinion changes, science keeps a consistent story. I am a Ph.D. student at UC Davis and a FFAR fellow.

I study gluten and celiac disease (CeD).

When I tell people this, I get a mixed bag of reactions. Many people are grateful for my research and hopeful that it can contribute to treatment development for gluten intolerances. On the other hand, I find that many of my colleagues can be dismissive of the need for CeD research, attributing it to a diet fad. I do my best to remain objective in my pursuit of knowledge, while still considering real peoples’ narratives. This was difficult for me at first. Early in my PhD, a professor asked what “the point” of my research was since celiac disease already has one very effective treatment: “just don’t eat gluten.” This sentiment threw me for a loop – maybe the avenue I was pursuing was aimless and unwarranted after all. It was only after some keen observation that I began to appreciate the complexity of the gluten-free landscape and the necessity for interdisciplinary research and robust scientific communication surrounding it.

As I became more interested in gluten intolerances, I started paying better attention to the ingredients in the food I was eating. It turns out that wheat is an incredibly popular additive to snacks that I previously assumed to be gluten-free. Even in food made without wheat, the threshold for immune reactions can be so low (~20 parts per million) that a very small source of contamination could render food inedible for someone with CeD. Then I started looking at the prices for gluten-free foods at my grocery store. Among the limited options, prices soared above those of conventional goods. What’s more, many of the gluten-free foods available were high in added starch and fat in an effort to emulate the physical properties of the missing gluten. It became clear to me that living with CeD could be risky, expensive and nutritionally inadequate. Perhaps “just” avoiding gluten wasn’t so easy after all.

It's Complicated...

I study wheat genetics, which aren’t quite like the pea plant pedigrees you may have learned about in high school biology. Whereas peas (and humans) inherit one copy of each gene from each parent (meaning everyone has two copies of each gene and is called “diploid”), wheat inherits three copies of each gene from each parent (so wheat has six copies of each gene and is called “hexaploid”). As you can imagine, this makes our Punnett squares quite a bit more complicated. Because “gluten” is really a word for many different types of wheat proteins, we have many different genes that encode “gluten.” Take these many different genes and multiply them by their six copies, and we are dealing with around a hundred different genes in one wheat variety (and there are many wheat varieties).

Mendel’s head would be spinning.

The human genetics of CeD aren’t so simple, either. We know some of the genes that predispose someone to get celiac disease, but we don’t completely understand why some people get it and some people don’t, or why their reactions are so different.

Taking all this together, we have a lot of different people and a lot of different gluten proteins that interact in a lot of different ways. While engineering a celiac-safe wheat variety is a great goal to shoot for, it will take a lot of time and effort- and the finished product will be a gluten-free cereal that lacks the structural integrity we value wheat for.

What can we do in the meantime? There is much to learn about the roles of different gluten proteins. Which are the worst triggers for CeD? Which are the most important for flour quality? By examining subsets of gluten proteins, we can get a better understanding of intermediate steps we can take within the larger objective of engineering celiac-safe wheat. For example, we recently found that knocking out a certain group of proteins, called the alpha-gliadins, can be beneficial both in terms of CeD reactivity and breadmaking quality. A win-win!

Takeaways

Conducting interdisciplinary research can feel like a “jack-of-all trades, master of none” situation...However, I find that having input from many lenses makes it possible to tackle previously unexplored questions. Maria Rottersman
FFAR Fellow, UC Davis

When scientists face complicated challenges, it can be easy to feel overwhelmed with the mountain of knowledge that might be relevant. Conducting interdisciplinary research can feel like a “jack-of-all trades, master of none” situation. I’ve certainly struggled with imposter syndrome as I scoop up semi-superficial understandings of plant biology, food science and human immunology as they relate to my project. However, I find that having input from many lenses makes it possible to tackle previously unexplored questions. To make this work, it’s necessary to be able to communicate with scientists from other fields and with people who may be directly affected by your research (in my case, CeD patients, bakers and farmers). As a FFAR Fellow, I am learning the skills to communicate with diverse groups and gaining the confidence to engage with them. It is well worth the effort.

Scientific Publications

Deletion of wheat alpha-gliadins from chromosome 6D improves gluten strength and reduces immunodominant celiac disease epitopes

Acknowledgements

I am incredibly grateful to the Foundation for Food & Agriculture Research and the matching funds from the Celiac Disease Foundation, which have made my research possible. I am also supported by the UC Davis Department of Plant Sciences. I appreciate the generous mentorship I receive from Dr. Natalie Kaiser, FFAR Fellow alum Dr. Dhruv Patel-Tupper, my principal investigator Prof. Jorge Dubcovsky and others in our lab.

ID: 1155, CA19-SS-0000000045

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