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Using transcriptomics in the face of climate change: are scientists generating more questions than a

“We can sequence genomes ‘til the cows come home, but that won’t give us an idea of what actually works.” An exasperated Dr. Line Bay from the University of Melbourne leans away from the conference table in the coral reef working group at a symposium hosted by UC Davis on a cold December Monday. She’s expressing what a lot of scientists feel right now: as our life-long research subjects disappear in front of our eyes, what can we even do?

Coral reef biologists face the sobering reality that almost all corals worldwide will disappear before 2040. In the last two years alone, reefs have lost 20% of their corals due to extreme bleaching events. Scientists are starting to realize that preserving what we have left is not enough. They are finding potential solutions in a relatively new field called “transcriptomics.”

Transcriptomics is the study of how organisms respond to a wide variety of stimuli at the cellular level. In the face of climate change, it is often touted as the golden goose of figuring out how to pluck tolerant species and individuals from the ecosystem before it’s too late. These animals and plants would be indispensable to conservation efforts in the future. They would also help to illuminate what makes an organism resilient to climate change. To the vast majority of scientists, this field is confusing, unattainable, and intriguing all at the same time. To a small minority, transcriptomics holds the key to understanding how and why individual animals respond to environmental stress like climate change. Within that minority, there are vehement defenders and exhausted deniers of transcriptomic research’s powers.

To see why this field is so important to understanding climate change, we have to look into the mechanisms of investigating the transcriptome. Say that a scientist finds a coral that is still thriving in a bed of bleached coral after a month of very warm temperatures. He might want to know why that one coral did so well when all others around it were dying. One way that corals can cope with warm temperatures is with a type of protein called a “heat shock protein”. These proteins are small capsules that gather up damaged proteins unraveled by heat, and refold them so that they can perform their functions again. If a cell has more heat shock proteins, it can refold more damaged proteins. More refolded damaged proteins mean that cells will retain more of their functions during heat stress. Therefore, scientists may think that a warm-tolerant coral has more heat shock proteins.

But how does a coral get more heat shock proteins? That depends on DNA and RNA, or the code of life. Transcriptomics focus on RNA, since RNA transcribes the instructions from DNA. Something interesting can happen at this step – RNA doesn’t just translate DNA directly to proteins; environmental stress or non-DNA-based regulatory functions can influence how much RNA is produced, which in turn influences how much of each protein is produced. The coral that does so well during warm temperatures may have more RNA expression of those heat shock proteins (more RNA expression = more of these beneficial proteins). Transcriptomics quantifies expression of RNA across as many of the animal’s functions as the scientist chooses. This extremely powerful tool would seemingly solve most questions about functions on the cellular level, but it isn’t that simple.

One of the greatest strengths of transcriptomics is also one of its biggest problems. Scientists have struggled to look deep into the cellular functions of animals and plants that aren’t of medical or agricultural interest due to impossibly high costs of genetic sequencing. With transcriptomics, this cost is reduced ten-fold. It becomes attainable to gather an incredible amount of information about a species that we previously knew nothing about – all for less than $10K. The biggest problem about this is the amount of information that is produced. There is no uniform way to organize, analyze, or interpret these data. It can become extremely overwhelming for scientists to jump headfirst into this field since they often find themselves asking more questions than they started with.

This dilemma of too much information is plaguing the transcriptomics field, bogging down any big discoveries to be made in the transcriptome alone. Dr. Eric Armstrong, a researcher working under Dr. Jonathon Stillman, a leader in the transcriptomics field, pointed to the challenges of gathering and analyzing the huge amount of data. “The field is always changing, I feel like I’m behind before I started,” said Dr. Armstrong in his office at UC Berkeley. Armstrong assembled and attempted to analyze the transcriptome of the porcelain crab with climate change stress, which included ocean warming and ocean acidification. He quickly realized why most labs hire a technician to sort out the major analyses after receiving the raw data from the sequencer: it was a lot of numbers. “If you don’t know what you’re looking for, it becomes impossible to find anything of substance,” he reflected, leaning back in his chair, illuminated by the lights of his tropical aquarium. Often transcriptomics require multiple follow-up studies to look at actual proteins, or to see how increased RNA expression can evolve in an organism. These follow-up studies can be expensive and time consuming, especially after drudging through the work of analyzing the transcriptome itself.

Transcriptomics felt like the magic end-all-be-all for many scientists, but too many studies are resulting in more questions and few answers. Part of this has to do with the types of scientists undertaking these studies – dealing with a mountain of data so large that it has to be stored on a supercomputer is not the average task for a lab- or field-based biologist. Computational biologists are much more suited for this type of work, but they aren’t the ones asking the questions. In this sense, transcriptomics is creating an opportunity for interdisciplinary work.

So how will scientists use transcriptomics to solve climate change questions on the short time scale that is required? If corals will be gone by 2040, they’re already behind. And that’s only one group of organisms in a world being impacted by a rapidly shifting climate.

The solutions to this predicament are slowly trickling into the main body of scientists working with this field. Transcriptomics is not the universal solution that scientists once thought it was, but it still is an extremely powerful tool in investigating the effects of climate change. In the last ten years, scientists have learned that it has to be a multi-faceted approach – looking at the transcriptome can’t be the only evidence gathered to solve a problem. As for whether scientists will continue doing this sort of work? There is no question that this powerful new method will find its place within the toolboxes of all types of scientists, especially as costs decrease. Transcriptomics is firmly rooted in the modern crisis of climate change biology, and any scientist overlooking the power of this field isn’t exploring potential biological solutions to their fullest extent.

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