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College Stories: Leslie Sieburth, Biology

Leslie Sieburth, Biology, the University of Utah

Associate Dean of Research

> June 26, 2018

The College of Science is pleased to announce the appointment of Professor Leslie Sieburth from the School of Biological Sciences as the new Associate Dean of Research in the College of Science, effective July 1, 2019.

Leslie earned her PhD in Botany from the University of Georgia, completed a postdoctoral appointment at the California Institute of Technology, and joined the University of Utah in 1999. Leslie’s research interests are plant developmental biology, especially as it relates to RNA decay and cell signaling. Leslie is a recipient of the prestigious University of Utah Distinguished Teaching Award and the College of Science Award for Teaching Excellence. She recently served as Associate Director of the School of Biological Sciences and serves on numerous University and school committees.

We are delighted that Leslie has agreed to take on the important role of Associate Dean of Research as the College moves to increase research capacity and productivity in the CoS.


Leslie Sieburth, Biology, the University of Utah

CoS Award for Teaching Excellence

> May 15, 2018

The CoS Award for Teaching Excellence recognizes extraordinary skill in university teaching with an emphasis on outstanding accomplishments and commitments to science and/or math education. This year, we express our appreciation to Leslie Sieburth who has excelled in challenging the intellectual curiosity of our undergraduates.


 

Leslie Sieburth, Biology, the University of Utah

Plant Genomics Yield Surprising Results

Discover Magazine - 2018

QUESTION:

How does RNA decay contribute to gene expression? Could the RNA decay rate be regulated on a molecular basis in order to control genetic traits?

Gene expression is typically measured as messenger RNA (mRNA) abundance, and changes in that abundance are usually attributed to transcription, or synthesis, of mRNA inside the cell. However,
RNA abundance is also influenced by its disposal, or degradation, but how degradation controls RNA abundance is not well understood.

WHO:

“My research uses a plant model, Arabidopsis thaliana, a small mustard plant, and we found that mutants with defects in mRNA decapping proteins experienced abnormal cell growth,” says Leslie Sieburth, Professor of Biological Sciences at the U.

“Our curiosity about why the mutants showed such poor growth led us to discover another mRNA decay enzyme, which we call SOV. We noted in our publication, in 2010, that most eukaryotic genomes encode a very similar protein, including humans,” says Sieburth.

A few years later, in 2013, scientists studying a human disorder called Perlman syndrome discovered that it was caused by mutations in the same gene. The gene, SOV, is known as DIS3L2 in humans.

Perlman syndrome is a genetic disorder associated with overgrowth in the size of the body or a body part of infants. The condition is almost always fatal prior to birth. The disorder has been grouped with Renal cell carcinoma and an increased risk for Wilms tumor.

Starting in 2014, Sieburth investigated how mRNA decapping and SOV/DIS3L2 contribute to decay of all mRNAs using genome-wide approaches.

“A fruitful collaboration with Fred Adler, a professor of biology and mathematics at the U, one of his graduate students, Katrina Johnson, and my postdoc Reed Sorenson, identified the decay rates of more than 17,000 mRNAs, and the contributions from decapping and SOV/DIS3L2,” says Sieburth.

One unexpected discovery was that the mRNAs that decay the fastest use the mRNA decapping pathway. A second discovery was that Arabidopsis mutants lacking an active SOV initiate a feedback pathway where the mRNAs – that are normally degraded by SOV – switch decay pathways, decay faster, and are also transcribed faster.

The results were published in Proceedings of the National Academy of Sciences (PNAS) in 2018.

FUNDING:

Research in the Sieburth laboratory is supported by four National Science Foundation (NSF) grants totaling nearly $2 million. The largest grant, titled, “The role of regulated degradation in controlling cytoplasmic mRNA levels,” focuses on mRNA decay pathways and enzymes, such as SOV. The funding will extend to 2020.

Sieburth recently received a new award funded through NSF’s Early-concept Grants for Exploratory Research (EAGER) program for her project, “Connecting RNA Molecular Kinetics to Developmental Regulation.”

Sieburth employs two undergraduate students, two graduate students – Alex Cummins and
Jessica Vincent – and one postdoctoral fellow, Reed Sorenson.

IMPACT:

Sieburth’s continuing genetic studies could provide new perspectives to fundamental cellular processes that are important in cancer biology and birth defects in humans.

In addition to research, Sieburth also is implementing new curriculum in the School of Biological Sciences. She is currently teaching a new class designed specifically for first-year students. The course, Fundamentals of Biology, is one part of a class sequence that includes two lecture-type classes and two laboratory classes.

“I led a curriculum reform committee, and along with nearly everyone in the School, have spent the past two years designing these courses, reading the literature to identify the instructional methods that have proven to lead to deep learning, and pulling together instructional materials,” says Sieburth. “We are a few months into the class now, and it is exciting to see that the students are engaged and learning.”

FUTURE:

Sieburth has three specific goals for the current NSF study, “The role of regulated degradation in controlling cytoplasmic mRNA levels.”

The first is to assess changes in mRNA decay rates in response to conditions where RNA abundance changes. Usually abundance changes are attributed to transcription, but few scientists have tested the contributions from RNA decay.

The second goal is to understand the feedback that occurs in SOV mutants in Arabidopsis.

Third, she wants to understand the basis for the wide range in mRNA decay rates, where half-life varies between 3.5 minutes and more than 24 hours. 


Unlocking the Mystery of Plant Communication

Salt Lake Tribune - 2011

Leslie SieburthPlants communicate. Maybe not to us or each other, but definitely to their own parts, relaying critical information the way our endocrinological systems circulate hormones.

This communication helps plants survive tough conditions. But it also inhibits growth, posing real challenges to food-production systems that want to coax crops out of plants even when they're stressed, according to University of Utah biologist Leslie Sieburth, who is looking for answers.

Her quest is to unlock the mechanism by which plants' roots tell leaves, "Hey, stop growing," when they are assaulted by pathogens, drought and other environmental pressures. Keeping crop plants productive while preserving their resilience will be crucial to supporting an expanding world population, expected to hit 9 billion by 2050, Sieburth says. Just a few weeks ago, it reached 7 billion.

"How will we feed 2 billion more people? Already we don't feed everyone effectively. Add to that climate change, that makes it more challenging," said U. science dean Pierre Sokolsky in introducing Sieburth to a recent gathering with Salt Lake City's business community.

Global warming is expect to result in more drought, pests that survive winters and an influx of pathogens, all conditions that will reduce cropland productivity. In the 1950s and '60s, the Green Revolution helped expand crop yields through fertilizers, pesticides and plant breeding. World population soon doubled, but yields have plateaued.

"Why can't we just keep that revolution going?" Sieburth said. Bugs have evolved resistance to pesticides, and fertilizer ingredients are scarce.

"Phosphorous is running out. Other costs are skyrocketing. Traditional plant breeding is very slow," Sieburth said. "We are losing farmland. Will we start growing food in our national parks? I would hate to see that happen."

One solution is a new Green Revolution that is smarter than the last one, she said.

"We need crops that survive in an uncertain climate. They will be genetically modified based on knowledge of molecular pathways," she said.

Leaves harvest solar radiation and convert it to sugar through photosynthesis, so processes that inhibit leaf growth depress yields. The revolution Sieburth envisions would interrupt these processes.

Several years ago Sieburth and her collaborators discovered the gene that enables signaling between roots and leaves in most land plants. Now they are trying to identify the molecule that carries the signal through the plant's vascular system and the protein that serves as a receptor on the cell walls in the leaves.

The idea is to "engineer" plants to keep their environmental triggers from turning off growth.

Prior research has determined that plant growth slows when only a single root is exposed to dry soil. Remove the dry root and growth rebounds.

"It triggers molecular events downstream that stops cells from dividing. We want to find out what that is," Sieburth said. Her collaborators include University of California Riverside geneticist Julia Bailey-Serres, a U. graduate, and her brother, Temple University chemist Scott Sieburth. The work is funded by the National Science Foundation and the U.S. Department of Agriculture.

Her experiments are conducted on thale cress, an ideal plant for use in labs because it is a compact self-pollinator that produces lots of seeds and its entire genome is known. The research got a big boost when Sieburth happened upon a mutant strain that overproduces the triggering molecule responsible for diminished growth. When they graft a mutant root to healthy plants, leaf growth stalls.

The team has determined the triggering molecule can pass through an agar block and is hoping to nail down its identity through bioassays.

"We are on the trail to finding it. When we find it we can find what is the stimulus," Sieburth said. But that's only half the story. Equally crucial is identifying the molecule's receptors that sit on the cell walls. There are 610 possible proteins, but Sieburth's team has narrowed the search to a handful of likely candidates.
If scientists can prevent these proteins from interacting with the signaling molecule, they might be able to figure out a way to keep crops plants both productive and healthy even when soils are dry and microscopic disease vectors attack. 


How Roots Control Plant Shoot

Science Daily - 2004

Leslie SieburthUniversity of Utah biologists discovered a gene that allows a plant’s roots to tell the leaves to stop growing, presumably when water is scarce, soil is too compacted or other conditions are bad.

While roots obviously carry food and water to the leaves, the new findings help show how roots also send chemical signals that control whether or not leaves grow. How leaves grow is a crucial matter given that leafy plants supply food for humans and other creatures, produce oxygen for all animals to breathe, influence global climate and grace us with the current season of brilliant fall colors.

"When we look at plants, it’s easy to think only about the above-ground parts you can see,” says Leslie Sieburth, who led the study and is an associate professor of biology at the University of Utah. “But this study shows that the roots potentially play a huge role – in addition to supplying water and nutrients – in controlling how the plant comes to look as it does. It’s very easy to ignore the root, but our study shows we shouldn’t.”

Manipulating the process someday might allow scientists to genetically engineer crops and other plants to be more productive in dry conditions – for example, so that crops could keep producing abundant leaves in a drought by irrigating them while overriding the genetic signal that normally would inhibit growth, Sieburth says.

The new study was published in the Oct. 5 issue of the journal Current Biology by Sieburth, graduate student Jaimie Van Norman and Rebecca Frederick, who formerly worked in Sieburth’s laboratory and now is a graduate student in biochemistry.

Seeking the Secrets of How Leaves Grow

Sieburth’s research focuses on a seemingly simple question: “How do leaves grow? It’s a basic biological question,” she says.

Plants look different depending where they grow. A dandelion, for example, may be very leafy in Florida’s humid climate, but have only small leaves when growing in Utah during a drought, says Sieburth.

She says the gene she and Van Norman discovered – named BYPASS1 or BPS1 – may be the key. BPS1 normally allows leaves to develop, but stops leaf growth when necessary, she adds. In the study, she and Van Norman demonstrated that BPS1 could be manipulated to change the way leaves develop even if a plant has enough food and water.

The study used a plant named Arabidopsis, commonly known as thale cress, which is frequently used in studies of plant genetics because it is small, easy to handle, lives only seven weeks from seed to seed, and fertilizes itself so mutant strains can be maintained as seeds. Most plants are believed to have genes similar to those in thale cress, which is related to broccoli, cauliflower, Brussels sprouts, cabbage and mustard.

Scientists already knew that a variety of hormones – cytokinin, abscisic acid and derivatives of compounds called carotenoids – play a role when plant roots send signals to shoots, which include everything above ground: stems, leaves, flowers and fruits. But little has been known about how genes active in roots control these chemical signals, Sieburth says. The new study reveals part of the answer, and indicates a previously unknown plant hormone – a chemical probably made from carotenoids – is involved.

Carotenoids include well-known substances such as beta carotene in carrots and tomatoes, lycopene in tomatoes, lutein in daffodil flowers and the substance that gives color and flavor to saffron, a spice from crocus flowers.

Details of the Experiments

In the study, the biologists discovered the BPS1 gene and then demonstrated that it is required to prevent a plant from constantly producing the carotenoid byproduct that turns off leaf growth.

First, they grew thale cress plants with the mutant form of BPS1 known as bps1. Normal seedlings produce an increasing number of flat, broad, round leaves as they grow. Mutants grew only two smaller leaves shaped like triangles or cones.

After a series of experiments suggested that the roots sent a signal to halt leaf growth, Van Norman did what Sieburth calls “a brilliant experiment.” She grew mutant seedlings, cut their roots off and placed the shoots on agar, a gelatinous substance containing nutrients. Those mutants produced two fairly normal flat leaves, then started making a third leaf that was small and abnormally shaped. Van Norman noticed that happened just as new roots started to grow from the bottom of the shoots.

So Van Norman kept cutting off the roots each time they started to regenerate. The plants produced normal leaves, indicating the mutant roots were sending a chemical signal to stop leaf growth.

To confirm that, Van Norman grafted mutant roots to normal four-day-old shoots.

“We got small leaves,” Sieburth says. “And no more were produced.”

The experiments indicated the normal BPS1 gene produces a protein that is a “negative regulator,” which Sieburth compares with the handle on a water faucet.

In a normal plant, BPS1 keeps the faucet shut. But when conditions are bad, it opens the faucet so that the growth-inhibiting carotenoid byproduct flows freely from the roots, telling leaves to stop growing.

Sieburth says the study didn’t demonstrate what those conditions might be, but lack of water and compacted soil are likely because such conditions would threaten the plant’s survival were it not for a signal telling the leaves to stop growing.

Earlier studies show that during drought, “an unknown signal comes from the root and restricts leaf growth,” Sieburth says.

Plants with mutant bps1 in the study also allowed the faucet to be wide open. That is why when roots were cut off repeatedly, the flow of growth-inhibiting hormone stopped and leaves grew normally.

Van Norman believes the normal BPS1 gene exists because “plants are immobile organisms. They have to be able to sense their environment both above ground and below ground, and then respond to changes in the environment.”

“They can’t just walk away,” when water is in short supply, Sieburth says.

Seeking the Chemical Signal

To indicate what kind of hormone turned off leaf growth, Van Norman and Sieburth treated thale cress plants with tiny amounts of a herbicide named fluridone, which inhibits production of carotenoids. When they used it on mutant plants – which otherwise would have stunted leaves – the leaves grew pretty much normally. Because fluridone stopped the growth-inhibiting chemical and allowed leaves to grow, and because fluridone inhibits carotenoids, the experiment suggested the growth-inhibiting chemical is a carotenoid.

Subsequent experiments indicated an unknown member of that class of hormones is responsible. Because a carotenoid named zeaxanthin made mutant plants even more abnormal, the researchers suspect the unknown chemical is derived from zeaxanthin.

Future studies will try to determine more about BPS1 functions, identify the specific growth-inhibiting carotenoid, learn precisely how the chemical halts leaf growth, and find out how plants in their normal environment use BPS1 and the anti-growth signal it unleashes.

Last Updated: 6/27/19