My summer with Monsanto

If you’ve ever talked to anyone passionately opposed to GMOs or modern agriculture, they’ve probably name-dropped Monsanto. A company smaller than Whole Foods would go bankrupt if their payroll included all the members of the USDA, EPA, FDA, AAAS, WHO, European Commission, and many more. Still, scientists echoing the conclusions of these organizations on the safety of certain agricultural practices sometimes get accused of acting as paid “shills”.

As such. I want to be very transparent about my own ties with the agricultural biotech industry. Over the next four and a half months, I will be interning part-time at Monsanto. An internship with a biotech company is both a requirement of the Designated Emphasis in Biotechnology Program at UC Davis and an excellent opportunity for me to explore future career options.

I will be working on Monsanto’s “BioDirect(TM)” project. In a nutshell, the goal is to figure out a way to use molecules of RNA to shut off genes in very specific insect or weed targets resulting in death of the pest. This technology would allow farmers to drastically reduce pesticide use and protect beneficial insects like ladybugs. It’s adaptable, so the recipe can be adjusted if resistance develops. And it’s compatible with no-till practices that protect soils from erosion.

My salary covers three days of work per week on this project exclusively. I spend the remaining two days a week on my dissertation research with the support of funding generously provided by the American Dissertation Fellowship from the American Association of University Women. Any outreach or science communication that I engage in occurs on a voluntary basis on top of my research.

When I asked a trusted faculty member at UC Berkeley if I should take a hiatus from any science outreach while on Monsanto’s payroll, she expressed frustration that I even had to ask this question. After speaking favorably about agricultural technologies on NPR, she got angry emails accusing her of being a “Monsanto shill”. When she asked where this was coming from, one accuser pointed at a $1000 award from the American Society of Plant Biology she received back in 1992. The award was sponsored by Monsanto. The company had no say in who was given the award or what was done with it. They simply provided the donation.

I’ve received two similar awards. One was the Monsanto Endowed Student Fund in Agricultural Biotechnology Award for $3000, granted to me by the Dean’s Office of the College of Biological Sciences at UC Davis in 2015. This award is given out every year and “is available to outstanding UC Davis, College of Biological Sciences, graduate students who are preparing for a career in agricultural biotechnology”. You can read my application for this award here.

I also received the Ginny Patin Memorial Scholarship for $2500 from the California Seed Association in 2016. You can read my application for this award here. In both cases, the funds were deposited into my account directly with no strings attached. These awards are displayed proudly on my CV/Resume as they are a badge of scholastic achievement.

The content of this post and every blog post or tweet I ever compose strictly reflect my own personal views and experiences and not the views of any of my employers past, present, or future, be they academic or corporate in nature.

Okay, so what the heck are “omics”?

In the National Academy of Science’s genetically engineered crop study report released a few days ago, they proposed a new regulatory framework for analyzing the safety of any crop variety that relies on a technology called “omics”? So what in the world is an omic and how is it useful?

There are many different types of “omics”. It all started with GENomics which involves figuring out and comparing the GENES between organisms. This has allowed scientists to identify different genetic “markers” associated with diseases and other traits. However, genomics are only part of the story. Just because a gene is present doesn’t mean it is active.

Active genes are used as a template to TRANSCRIBE molecular messengers called RNA. Analyses of the levels of RNA within an organism in a given tissue or in response to a certain stimulus are known as TRANSCRIPTomics, but it doesn’t stop there.

RNA transcripts serve as instructions that enable cells to build PROTEINS. Proteins are the real workhorses of the cell, and are largely responsible for an organism’s traits. Comparisons of the protein landscape in an organism are accomplished by PROTEomics.

But what about all the other cool stuff floating around in cells? Hormones, pigments, vitamins, ethanol? These molecules are assembled within cells and are called METABOLITES (and plants have way way way more of them than people: nicotine, caffeine, capsaicin…..). And guess what? Where there’s a molecule there’s an “omics”, so now we’ve got METABOLomics.

So omics includes the study of the genes, RNA, proteins, and metabolites in an organism (there are even more, but I won’t go there). Sound complicated? It gets worse. When scientists gather data for omics studies, they get it in pieces.

So you know the human genome project? It’s not like somebody scanned a human blood sample and printed out the entire genome. To put it into perspective, if the human genome was unravelled and blown up to the diameter of a strand of hair, that hair would be 30 miles long and form a wad the size of a volleyball.

The genome had to be sequences piece by piece (not particularly systematically) and then those pieces had to be reassembled. To put it into perspective, Dr. Keith Bradnom uses the following analogy: Take 100 identical jigsaw sets, mix all the pieces together, throw away 10% of the pieces, randomly mix in the contents of an unrelated puzzle, throw away the cover of the box, and assemble!

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Some scientists on twitter even called this analogy an over-simplification! As you can imagine, this takes not only a lot of brain power, but also a lot of computing power. Then once you finally get it assembled….

austin

So that’s why the National Academy of Sciences said that we need to further develop these technologies. The idea is that we could compare the “omics” between new crop varieties and existing varieties and analyze any significant differences for potential safety concerns. As you can see, this is no small project, and that’s why they call it “big data”.

If you are a non-scientist, I hope you found this explanation helpful. If you are a scientist, particularly a computational scientist, please let me know in the comments if I’ve made any mistakes or am missing important details.

Whatcha gonna do with all that junk-all that junk inside them genes?

Imagine if all the music on itunes was interrupted by blocks of white noise that you had to manually edit out every time you downloaded a song. Makes no sense right? Why would songs be recorded that way? Why not just remove the junk at the source, so you don’t have to waste time and energy?

That’s exactly what scientists wondered when they discovered genetic material known as introns. Genes are regions of DNA that are used as templates to make molecular messages called RNA. RNA provides instructions to make the proteins that determine an organism’s traits. This process, called “gene expression” is the “central dogma” of molecular biology. Before RNA is used to make proteins, large sections called introns are removed. The remaining sections, which actually contain the genetic information, are spliced back together.

Central Dogma

GENE EXPRESSION: In a process called transcription, DNA is used as a template to make an RNA message. Regions of the RNA known as “introns” are cut out, and the remaining pieces are spliced back together to yield mature RNA. The mature RNA message is then used as instructions to build a protein in a process called translation.

Introns, originally called “junk DNA“, are not present in the mature RNA and do not influence the final protein product. So why do cells waste energy, copying introns just to remove them immediately afterwards?

Returning to the music analogy, imagine itunes gives in to complaints and removes the white noise. Customers are surprised to find that suddenly some songs are not downloading as efficiently. Some can only be downloaded a few times per day, others will not download at all, and the most popular songs are hit the hardest

That’s what happens when scientists try to express genes without introns. For many genes, the intronless version does not yield as many copies of RNA. Further, some genes are completely dependent on this “intron-mediated enhancement” or “IME”. Only certain introns exhibit IME, and they tend to be found in the most fundamental genes, those that are expressed all the time.

IntronDependent

Certain introns can increase expression of some genes to varying degrees. This figure shows three plant seedlings that all contain a gene that encodes a protein that makes a blue dye. The blue dye gene in the plant in the middle does not contain an intron. In each of the other plants, the blue dye gene contains a different intron. This work was completed by a previous student in our lab and is published in Plant Biotechnology Journal.

IME can increase the expression of genes anywhere from 2 to 20 fold in plants, animals, and fungi. In my lab, we study IME in plants, because introns are routinely used to increase expression of genes in crops from herbicide-tolerant soybeans to nutritionally enhanced rice. Better understanding IME could enable us to design synthetic introns that maximize gene expression potential.

Despite the obvious utility of IME, little is known about the mechanism. What we do know doesn’t fit conventional models of gene expression. For example, in order to exhibit IME, the intron must be very close to the start of the gene. Remarkably, if an IME intron is inserted into a gene that is usually only expressed in certain tissue, it can cause that gene to be expressed everywhere. New data shows that IME can even influence the length of an RNA message and act independent of DNA regions normally thought to be essential for expression.

If you want to dig deeper, my advisor Dr. Alan Rose and I published a review on the topic aptly titled “the enduring mystery of intron-mediated enhancement”. You can access the full-length PDF and a video summary on my publications page.