Bond LSC

Unlocking plants’ metabolic thermostat — award-winning LSW posters

Unlocking plants’ metabolic thermostat — award-winning LSW posters

Matthew Salie would like to see chubbier plants.

“You’ve probably never really seen a fat plant before, right?” said Salie, a fourth year MU graduate student in biochemistry­. “Humans, we make plenty of extra fat and store that as energy. But plants don’t really need to do that — they make just as much as they need, and that’s about it.”

Salie studies plant metabolism with Bond LSC researcher Jay Thelen, an associate professor of biochemistry. He’s one of 25 winners honored for research presented during Missouri Life Sciences Week 2015.

The Thelen lab looks for ways to increase the amount of vegetable oil that crops such as corn and soybean can produce. Salie focused on an enzyme that is the first step in the pathway to producing fatty acid in plants.

The idea was that if he could reduce metabolic limits at the beginning of the process, then the downstream production of oil would increase.

“I found these new proteins that no one has ever really studied before,” Salie said. “As I started to look into them over the last year or two, it turns out that they actually seem to incorporate themselves into the enzyme and slow down it’s activity.”

Four separate proteins normally combine to form the functional enzyme, but the new proteins Salie identified mimic those components and can take their place, like a cuckoo bird replacing another species’ eggs with its own. The more mimics that replace proteins, the fewer functional enzymes the plant produces, which means less oil.

It’s a simple, nuanced way for the plant to fine-tune the production of fatty acids.

“Instead of being an on-off switch, it’s more like a thermostat,” Salie said. And if he can adjust that thermostat in a plant, it should start packing on the pounds.

Although Salies work was only recently submitted for publication, it’s already receiving recognition. His poster, “The BADC proteins — a novel paradigm for regulation of de novo fatty acid synthesis in plants,” won first place in the Molecular and Cellular Biology category during the Life Sciences Week poster competition in April.

Salie relished the opportunity to share his findings with researchers and non-scientists alike.

“It’s a great experience, because it helps you realize what’s really important about the work that your doing,” he said. “It also really encourages you to work harder. It’s like, ‘Wow, this is actually meaningful stuff!’ which can be hard to see when you’re working 60 or 70 hour weeks at the lab, just sitting there by yourself.”

Salie was among more than 300 students who presented their research during the 31st annual Life Sciences Week poster sessions.

 

The winners in each of the five categories are:

  • Molecular and Cellular Biology
    • Matthew Salie, Matthew Muller, Stephanie Bowers
  • Organismal Biology
    • Miqdad Dhariwala, Ryan Sheldon, Carine Collins
  • Genetics, Evolution and Environment
    • Julianna Jenkins, Nathan Harness, and a tie for third between Sharon Kuo and Susheel Bhanu Busi
  • Life Science and Biomedical Engineering Technologies and Informatics
    • Jamie Hibbard, Hang Xu, Brittany Hagenhoff
  • Social and Behavioral Sciences
    • Vaness Cox and Ian George tied for first place

Undergraduate winners are Vincent Farinella, James Mrkvicka, Anette van Swaay, Romanus Hutchins, Dallas Pineda, Kelsey Boschert, Anthony Onuzuruike, Clare Diester, Adam Kidwell and Sean Rogers.

Honorable mention:

  • Social and Behavioral Sciences
    • Undergrad Honorable Mention – Kelsey Clark
    • Undergrad Honorable Mention – Louie Markovits
  • Genetics, Evolution, and Environment
    • Grad Honorable Mentions: Megan Murphy (Schul) and Amanda Smolinsky (Holliday)
    • Undergrad Honorable mention: Anthony Spates (Holliday)
  • Organismal Biology
    • Grad Honorable Mention: Kathleen Pennington
    • Grad Honorable Mention: Kasun Kodippili
    • Grad Honorable Mention: Christopher Tracy
    • Undergrad Honorable mention: Chelsie Todd
    • Undergrad Honorable mention: Holly Doerr
    • Undergrad Honorable mention: Zeina Zeida
  • Molecular and Cellular Biology
    • Grad Honorable mention, Khalid Alam [Burke lab]
    • Grad Honorable mention, Zhe Li [Sarafianos lab]
    • Undergrad Honorable mention: Vincent Markovitz [Guo lab]

Additional prizes were awarded for communication prowess and poster design chops.

For photos of some of this year’s winner, check out this Flickr album

Oliver Rando researches effect of fathers’ lifestyles on their children

How much does a newborn know about the world?

That can depend on their parents’ genes, according Oliver Rando, an epigeneticist at the University of Massachusetts.

Rando will speak Saturday, March 14, at 10:30 a.m. at the 11th Annual Life Sciences and Society Program at Bond LSC. His research focuses on how fathers’ lifestyles affect their children, one part of the symposium’s focus on epigenetics. Epigenetics is the study of how organisms change because of a modification in gene expression.

Rando is clear that his research is no more important than that of other scientists in his field.

“The field we work in is important since we and others have shown that a father’s lifestyle can potentially affect disease risk and other aspects of his children,” he said.

During his talk on Saturday, Rando will discuss a “paternal effect paradigm” based on experiments his lab conducted on male mice. The mice were fed different diets and mated with control females. Then researchers analyzed the metabolic effects that resulted in their offspring.

“In terms of the basic science aspects of the system, doing this sort of experiment with fathers rather than mothers is important, since mothers provide both an egg and a uterus to the child, whereas in many cases fathers only provide sperm,” Rando said. “So, with fathers you don’t have as many things to look at to find where the relevant information is.”

Scientists in his lab also study yeast and worms to understand epigenetic inheritance. They use molecular biology, genetic and genome-wide techniques to conduct the research.

For more information about Dr. Oliver Rando, read this Q&A from the Boston Globe.

Find more information about LSSP events and speakers at http://lssp.missouri.edu/epigenetics.

Holding on: Bond LSC scientist discovers protein prevents release of HIV and other viruses from infected cells

Shan-Lu Liu and Minghua Li, HIV Research at the Bond Life Sciences Center

Shan-Lu Liu, Bond LSC scientist and associate professor in the MU School of Medicine’s Department of Molecular Microbiology and Immunology. Courtesy Justin Kelley, University of Missouri Health System.

Shan-Lu Liu initially thought it was a mistake when a simple experiment kept failing.

But that serendipitous accident led the Bond Life Sciences Center researcher to discover how a protein prevents mature HIV from leaving a cell.

Proceedings of the National Academy of Sciences published this research online Aug. 18.

“It’s a striking phenomena caused by this particular protein,” Liu said. “The HIV is already assembled inside the cell, ready for release, but this protein surprisingly tethers this virus from being released.”

The TIM – T-cell/transmembrane immunoglobulin and mucin – family of proteins hasn’t received much attention from HIV researchers, but recent research shows the protein family plays a critical role in viral infections.  From Ebola and Dengue to Hepatitis A and HIV, these proteins aid in the entry of viruses into host cells.

But its ability to stop the virus from leaving cells remained unknown until now. Liu’s lab stumbled onto this finding in November 2011 when trying to create stable cells for a different experiment. After two months of troubleshooting the HIV lentiviral vector – where genes responsible for creating TIM-1 proteins were inserted into a cell to create a stable cell line that expresses the protein – Liu was confident the vector’s failure was not only interesting but also important.

Shan-Lu Liu and Minghua Li, HIV Research at the Bond Life Sciences Center

Minghua Li, coauthor of the study and an MU Area of Pathobiology graduate student. Courtesy Justin Kelley, University of Missouri Health System.

The lab spent the next two years trying to figure out what was happening. Minghua Li, an MU Area of Pathobiology graduate student, carried out experiments that confirmed the protein’s power to inhibit HIV-1 release from cells, reducing normal viral infection. His experiments showed TIM proteins prevent normal deployment of HIV, created by an infected cell, into the body to propagate.

TIM proteins stand erect like topiary on the outside and inside surfaces of T-cells, epithelial cells and other cells. When a virus initially approaches a cell, the top of each TIM protein binds with fats – called phosphatidylserine (PS) – covering the virus surface. This allows a virus, such as Ebola virus and Dengue virus, to enter the cell, infect and replicate, building up a population inside.

But as the virus creates new copies of itself, the host cell’s machinery also incorporates TIM proteins into new viruses. That causes problems for HIV as it tries to leave the cell. Now these proteins cause the viruses to bind to each other, clumping together and attaching to the cell surface.

“We see this striking phenotype where the virus just accumulates on the cell surface,” said Liu, who is also an associate professor in the MU School of Medicine’s Department of Molecular Microbiology and Immunology. “We consider this an intrinsic property of cellular response to viral infection that holds the virus from release.”

This model shows the  interaction between TIMs and PS among the round HIV virions, as well as that between viral producer cells. This collectively leads to accumulation of HIV virions on the plasma membrane on the outside of the cell. Courtesy Mingua Li.

This model shows the interaction between TIMs and PS among the round HIV virions, as well as that between viral producer cells. This collectively leads to accumulation of HIV virions on the plasma membrane on the outside of the cell. Courtesy Minghua Li.

Further research is needed to determine overall benefit or detriment of this curious characteristic, but this discovery provides insight into the cell-virus interaction.

“This study shows that TIM proteins keep viral particles from being released by the infected cell and instead keep them tethered to the cell surface,” said Gordon Freeman, Ph.D., an associate professor of medicine with Harvard Medical School’s Dana-Farber Cancer Institute, who was not affiliated with the study. “This is true for several important enveloped viruses including HIV and Ebola. We may be able to use this insight to slow the production of these viruses.”

The National Institutes of Health and the University of Missouri partially supported this research. Additional collaborators include Eric Freed, PhD, senior investigator with the National Cancer Institute (NCI) HIV Drug Resistance Program; Sherimay Ablan, biologist with the NCI HIV Drug Resistance Program; Marc Johnson, PhD, Bond LSC researcher and associate professor in the MU Department of Molecular Microbiology and Immunology; Chunhui Miao and Matthew Fuller, graduate students in the MU Department of Molecular Microbiology and Immunology; Yi-Min Zheng, MD, MS, senior research specialist with the Christopher S. Bond Life Sciences Center at MU; Paul Rennert, PhD, founder and principal of SugarCone Biotech LLC in Holliston, Massachusetts; and Wendy Maury, PhD, professor of microbiology at the University of Iowa.

Read the full study on the PNAS website and browse the supplementary data for this work. See more news on this research from the MU School of Medicine.