Office of Research for Undergraduate Director Joe Johnson, Coordinator of Undergraduate Research Martha Weber, and two other personnel stand in front of a banner that reads "Miami Undergraduate Research Forum."

Video describes research presented at Miami University’s 2016 Undergraduate Research Forum

This video offers an overview of the role students have played in the research of Miami University biology professor Katia Del Rio-Tsonis. This research was presented at Miami’s 2016 Undergraduate Research Forum, which was held April 27.


Video by Miami University College of Arts & Science, with thanks to Jason Barone, College Director of Communications. Photo of Office of Research for Undergraduates staff by Scott Kissell, Miami University Photo Services.

Three women pose in front of a Hilton hotel.

Biologist helps explain why cardiovascular health tends to vary by sex

A woman stands in front of a very large poster. She points to her name -- Minqian Shen -- within a long list of names. Visible text: ENDO. 2015 Abstract Awards and Travel Grants. Early Career Forum Travel Awards. Supported by the Endocrine Society. These application-based travel awards are presented to graduate students, medical students, postdoctoral fellows, and clinical fellows in endocrinology. 125 travel awards supported by the Society; 2 additional travel awards supported by Women in Endocrinology.
Minqian Shen, a graduate student of Dr. Haifei Shi, points to her name on a list of students who received Early Career Forum Travel Awards for the 2015 Endocrine Society Annual Meeting.

There are a number of reasons women tend to live longer than men. One of them is cardiovascular disease – on average, women develop it about a decade later than men. The female hormone estrogen seems to play a role, by keeping women’s arteries healthier until menopause. But Haifei Shi, an associate professor of biology at Miami University, thinks brain-derived neurotrophic factor (BDNF) may also play a role.

BDNF is a protein that helps sustain existing neurons and encourages the development of new neurons and synapses in the brain and central nervous system of humans and other mammals. In her lab, Shi has found that exposing rats to BDNF causes them to eat less and exercise more.

Assuming the same thing is true in humans, BDNF could one day be used in therapeutic treatments to help control obesity, which is a major risk factor for the development of cardiovascular disease.

But to develop safe and effective treatments, scientists need to better understand how BDNF works in the nervous system, and how it might work differently for male and female patients.

Shi is contributing to this understanding by studying rats. She has found that female rats are more sensitive to BDNF than male rats are. That is, it takes less BDNF to produce an advantageous ratio of food consumption to energy expenditure in a female rat than it takes to produce the same advantageous ratio in a male rat. She says this suggests that any BDNF-based drug therapies should be developed with gender-specific dosing in mind.

Dosing isn’t the only consideration, though. The route of delivery is also important. According to the FDA, there are some 100 ways of introducing a drug into the body, everything from auricular (by way of the ear) to oral (by way of the mouth) to subcutaneous (injected under the skin). The form a drug comes in – say, ear drops, pills, or injections – influences how quickly it is released into the system, how it is distributed throughout the system, and how quickly it is absorbed and eliminated. Those things can have a huge effect on the safety and efficacy of a specific treatment.

To determine the optimal route of delivery for a BDNF-based drug, Shi says it’s important to find the parts of neural circuit in the autonomic nervous system that BDNF activates, including brain nuclei, ganglia cells, and nerve terminals.

“If BDNF activates different parts of these neuralcircuits in males than in females,” she says, “then the targeting sites and route of delivery for any future drugs could be different as well.”

Shi plans to study this question using funds from a $390,150 grant she recently received from the National Institute of Diabetes and Digestive and Kidney Diseases, which is part of the National Institutes of Health (NIH).

“Given how difficult it is to receive funding from NIH right now, at first I was not sure if I could get funding,” Shi says. “When they sent me the award notice I felt very fortunate.”

She was also gratified to find that the program officer and every member of the NIH panel that reviewed her grant proposal characterized Miami’s research climate as excellent.

Contributing to that excellence, Shi says, are the research facilities and internal funding support provided by the Department of Biology, the College of Arts and Science (CAS), and the University Senate’s Committee for Faculty Research (CFR). She has received the Madalene and George Shetler Diabetes Research Award from the CAS and two CFR Faculty Research Grants – one in AY2009-2010 and one in AY2013-2014. These awards helped her gather preliminary data that enabled her to demonstrate the potential of her work in applications to the NIH and other funding agencies, including the American Heart Association.

Shi’s most recent NIH grant uses the R15, or Academic Research Enhancement Award (AREA), mechanism. Consistent with this program’s goal to expose students to research, Shi plans to involve students in all aspects of her current study, just as she did with a previous AREA grant study. Graduate students Xian Liu, Minqian Shen, and Qi Zhu and undergraduate students Annie Davis and Anjali Prior will help design, troubleshoot, and carry out experiments. They will collect data, run analyses, write manuscripts, and present results at local, national, and international conferences.

Davis, a sophomore double majoring in premedical studies and public health, attended the international meeting of the Society for the Study of Ingestive Behavior with Shi and graduate students Xian and Minqian in Denver this past July.

“Annie learned so much. I think it was really good exposure for her,” Shi says. “In the future, I’d like to take more students to this and other conferences.”

Given Shi’s continued success, not only in doing research, but also in securing funding to support it, that seems a likely prospect.

Written by Heather Beattey Johnston, Associate Director & Information Coordinator, Office for the Advancement of Research & Scholarship, Miami University.

Photo of Xian Liu, Haifei Shi, and Minqian Shen courtesy of Haifei Shi. Photo of Minqian Shen courtesy of Haifei Shi.

With new program, NIH tests change in how it funds research

The future of biomedical research in the U.S. depends in part on the way the National Institutes of Health (NIH) fund projects and researchers.
The future of biomedical research in the U.S. depends in part on the way the National Institutes of Health (NIH) fund projects and researchers.

In a recent post on the NIGMS Feedback Loop blog, director of the National Institute of General Medicine Sciences (NIGMS) Dr. Jon Lorsch acknowledged the need for changes in the way the National Institutes of Health (NIH) funds biomedical research.

In his post — titled “A Shared Responsibility” — Lorsch cites evidence that suggests that “funding smaller, more efficient research groups will increase the net impact of fundamental biomedical research: valuable scientific output per taxpayer dollar invested.”

Stating things bluntly, Lorsch says, “In the current zero-sum funding environment, the tradeoffs are stark: If one investigator gets a third R01, it means that another productive scientist loses his only grant or a promising new investigator can’t get her lab off the ground. Which outcome should we choose?”

Lorsch puts the NIGM’s new Maximizing Investigators’ Research Award (MIRA) program forward as a possible solution. According to the Funding Opportunity Announcement (FOA), the MIRA program aims to:

  • Increase the stability of funding for NIGMS-supported investigators, which could enhance their ability to take on ambitious scientific projects and approach problems more creatively.
  • Increase flexibility for investigators to follow important new research directions as opportunities arise, rather than being bound to specific aims proposed in advance of the studies.
  • More widely distribute funding among the nation’s highly talented and promising investigators to increase overall scientific productivity and the chances for important breakthroughs.
  • Reduce the time spent by researchers writing and reviewing grant applications, allowing them to spend more time conducting research.
  • Enable principal investigators to devote more time and energy to mentoring junior scientists in a more stable research environment.

Currently, MIRA is a pilot program limited to a small group of eligible applicants (to determine if you’re eligible, consult this flowchart), with letters of intent due April 20, 2015 and full proposals (including a “Research Strategy” section limited to six pages) due May 20, 2015. If the pilot is successful, NIGMS plans to issue additional FOAs open to additional groups of investigators.

Answers to frequently asked questions about the MIRA program can be found here.

Photo of NIH Building 1 by unknown photographer (public domain), via Wikimedia Commons.  Aerial photo of NIH campus by National Cancer Institute (public domain), Via Wikimedia Commons.

Giant model of the DNA double helix at a science museum in Ann Arbor. The helixes sides are pearlescent white tubes that twist in toward the center of the frame from the middle left. The "rungs" between the sides are red, blue, green and brown tubes connected by slimmer copper-colored tubes.

Scientist turns to crowd to fund research

Image is a screenshot of a webpage on experiment.com. At the top of the image is the "experiment" logo, a search box, and three links: "Discover," "How It Works," and "Sign up or Login." In the center of the image is a picture of a frozen North American wood frog. Laid over the picture of the wood frog is a screened dark grey box with the words, "Unlock the Secrets of Animals that Survive Freezing! Andor Kiss Miami University." Next to that box is another, white box that shows the progress of the project's funding. "$3,031 Pledged" appears in large type at the top of the box. Underneath that, a green bar stretches from margin to margin. Below the green bar are the following words: "101% Funded $3,000 Goal 0 Days." A smaller grey box appears below the funding "thermometer." The text in it reads, "Success! This project was funded on: 8 November 2014." Below the picture of the frog are navigation links: "Overview," "Abstract" (this is the one highlighted), "Lab Notes (12)," and "Comments (20)." Below that are three columns of text. The heading on the first column is, "What is the context of this research?" Below that heading is the following text: "The North American wood frog is an animal that has adopted a strategy of overwintering by burrowing to the leaf litter and other forest floor material and freezing. The frog can do this by flooding its blood with glucose and urea and other small molecules. The glucose acts in a similar manner to antifreeze, and the urea." The remaining text is cut off. The heading on the second column is: "What is the significance of this project?" Below that heading is the following text: "The wood frog is an example of a vertebrate animal who can undergo freezing and survive. One of the biggest problems with human organ transplants are the incompatibility and unavailability of the correct organ to correct recipient within a critical time frame. If we could freeze and/or chill preserve organs, we could save." The remaining text in this column is cut off. The third column heading is: "What are the goals of the project?" Below that heading is the following text: "I have wood frog tissue and the all the necessary skills and equipment to isolate, sequence, assemble and annotate the wood frog genome. If funded, I will: (1) Isolate the genomic DNA of the North American wood frog." No more text in that column is visible.
Miami University adjunct assistant professor and supervisor of the Center for Bioinformatics & Functional Genomics, Dr. Andor Kiss, received the funding he needed to sequence the genome of the North American wood frog on the crowdfunding site experiment.com

Once the domain of musicians, filmmakers, and tech innovators, crowdfunding is beginning to capture the attention of scientific researchers like Andor Kiss, adjunct assistant professor and supervisor in Miami University’s Center for Bioinformatics & Functional Genomics (CBFG).

When Kiss needed a relatively small amount of money – $3,000 – to purchase some genome sequencing technology, he knew he’d have to think outside the box of federal funding because most of those agencies are limited in their ability to fund a project with such a small budget.

The genome Kiss wants to sequence is that of the North American wood frog (Rana sylvatica). He and other Miami researchers are interested in this organism because of its ability to freeze in winter, and then resume normal function after thawing in the spring.

“Very few vertebrates have the capacity to freeze and survive,” Kiss says.

Past media coverage of Miami researchers’ work on the wood frog (including this post and this episode of PBS’s science program, NOVA), reflected public fascination with the amphibian’s seeming superpower, and that’s what Kiss banked on for funding his genome-sequencing project

“I thought, ‘Well, because of the inherently attractive nature of this particular organism in capturing the public’s imagination, maybe I could crowdfund this and get a significant chunk of people who are interested in science to do this,’” Kiss recalls.

In the end, 41 backers donated a total of $3,031 – 101% of the goal – to Kiss’s project through Experiment, a site that Bill Gates has said “helps close the gap for potential and promising, but unfunded projects.”

The victory was hard-won.

“You have to work at it,” Kiss says of this kind of crowdfunding. “You have to tweet about, it. You have to do an ‘Ask Me Anything’ on Reddit. You have to really work the Internet hard, because a lot of people are not going to find it on their own. You have to contact colleagues, go to meetings, talk to people who are interested.”

The donated funds, coupled with a discount from the manufacturer, have allowed Kiss to purchase an Illumina Tru-Seq Synthetic Long-Read DNA Kit.

With this kit, Kiss hopes to answer two questions about Rana sylvatica:

  • Does this frog have the same genes every other frog has, but expresses them in a unique way?
  • Are there certain genes unique to this frog?

But even if he doesn’t get the answers he’s looking for, Kiss says his crowdfunders’ investment won’t be wasted.

“I would be extremely surprised if we didn’t find novel and unexpected things with the assembly of this wood frog genome,” he says. “But let’s just assume that’s the worst case scenario: we don’t find anything about the wood frog per se. At least we have developed a technology here at the CBFG that we can apply to other projects. Gaining this technical capability is a very good, valuable goal.”

Just the same, it’s the very uncertainty of a project that can make it an ideal candidate for crowdfunding. For some investors, the prospect of funding a project that could one day lead to a major discovery or innovation is thrilling, and since the stakes are usually small – the average donation to Kiss’s project was about $74 – not much is lost if the project hits a dead end.

That’s good news for scientists like Kiss, who can find it difficult to get projects that are risky or exploratory through the peer review process at government funding agencies, including the National Science Foundation (NSF) and the National Institutes of Health (NIH).

Miami University’s Associate Provost for Research & Scholarship, Jim Oris, anticipates crowdfunding will play an increasingly important role for scientists, innovators, and creators at universities.

“Social media has broken down and worked around hierarchies in many industries, removing gatekeepers and letting many more voices through,” Oris says. “Crowdfunding has the potential to do the same for research and creative activity at universities.”

To facilitate grassroots investment at Miami, Oris is leading the development of a homegrown crowdfunding platform. The yet-to-be-named system will allow Miami students, faculty, and staff to register projects and set a funding goal.

“We’re still very much in the beginning stages of developing the system, and there are many details to be worked out,” Oris says. “But the goal is to engage Miami alumni, family, and friends from around the world by offering them an opportunity to have a meaningful and measureable impact on work happening at Miami today.”

Kiss agrees that the measurability inherent in crowdfunding campaigns – fundraising “thermometers” are a hallmark of virtually every platform – is part of their appeal.

“People like to donate to a specific target,” he says. “They like being able to point to something concrete and say, ‘I contributed to that.’ And if the goal is to raise $2,500, there’s no question that a $100 donation will make a difference.”

Today, investors in Kiss’s wood frog genome project can point to equipment in the CBFG and say, “I contributed to that.” But Kiss hopes one day they’ll be able to point to more.

“Nature has already solved a lot of the problems. We just have to figure out how nature did it. Once we’ve sequenced the genome of the wood frog, we may eventually be able to read nature’s instructions to improve organ transplants and other medical treatments.”

Written by Heather Beattey Johnston, Associate Director & Information Coordinator, Office for the Advancement of Research & Scholarship, Miami University.

DNA model image by Alfred Hermida, via Flickr, used under Creative Commons license.

A hand wearing a purple glove holds a cylindrical, transparent hydrogel in its palm. In the background, more hydrogels rest in petrie dishes and various metal instruments are on a parchment-colored tray.

3D printing is a promising new dimension in medicine

Two women in white lab coats are focused on and touching a piece of machinery on a tabletop. The machine is made primarily of white plastic, but also has some metal parts, and it has some cables extending out from it. The woman in the left of the frame has long, dark blonde hair. She is seated and wears glasses. The other woman stands to the first woman's left. She also wears glasses and has short, dark hair.
Master’s student Martha Fitzgerald (left) and Dr. Jessica Sparks, associate professor in chemical, paper, and biomedical engineering, conduct research to create lifelike tissues with a 3-D printer.

Painful pressure ulcers often afflict the elderly and people with limited mobility. Better known as bedsores, these ulcers sometimes lead to life-threatening complications and can be costly to treat.

“They’re something that all long-term care facilities want to prevent in any way that they can,” says Jessica Sparks, an associate professor in the department of chemical, paper, and biomedical engineering at Miami University.

Sparks is collaborating with Miami nursing faculty Deborah Beyer and Brenda Barnes ’82 on a proposal to develop pressure ulcer models that are realistic in color and shape.

Their proposal involves additive manufacturing (AM) technology. AM — often referred to as 3-D printing — uses three-dimensional design data to deposit successive layers of metal, plastic, or other material until a three-dimensional solid item is complete.

“We’re going to use the models to train the frontline staff, who would be the most likely to see a very early-stage pressure ulcer developing on a patient,” Sparks says.

Those staff members could then call in a wound care specialist to administer treatment before the condition progresses.

“Using 3-D printing in the field of medical simulation for training has lots of potential,” Sparks says. “Those two things should go together.”

Sparks, Beyer, and Barnes plan to request funding for their project from the Ohio Board of Regents’ Workforce Development and Equipment Facility program within the next two years. They are encouraged that recent conversations with a large regional hospital and wound care specialists at the Veterans Affairs health system have generated enthusiasm for this work.

“Their response makes it clear there’s good potential demand for what we’re trying to create,” Sparks says. “I’m confident we’ll have a good test platform for this technology.”

As valuable as models like this are for training, Sparks thinks they’re just beginning to tap into AM technology. With pressure ulcers, she explains, patient-specific anatomy is less important.

The same is not true for other clinical applications, such as a tumor with a specific geometry. In those situations, surgeons need to be able to practice with 3-D models that resemble the real tumor as much as possible, Sparks says.

Commercially available AM equipment can use anatomical data from a CT scan or an MRI to print the type of patient-specific training models Sparks envisions for surgeons. But, these models lack tissue-like mechanical properties.

“Some 3-D printers can print in flexible materials,” Sparks says, “but those materials don’t do a great job of mimicking biological tissue.”

Sparks wants to change that. Aided by a research incentive grant from Miami’s Office for the Advancement of Research & Scholarship, she and her biomedical engineering colleagues Jason Berberich and Justin Saul are developing new 3-D printing platforms. They use materials that look and feel more like human skin, muscle, blood vessels, and other soft tissue.

The research incentive grant also supports the work of research assistant and master’s student Martha Fitzgerald ’13, who plans to write her thesis on the techniques she has helped develop.

Together with Sparks and Berberich, Fitzgerald has written an oral presentation that she will deliver at the Biomedical Engineering Society national conference in October, an “excellent opportunity for Martha,” Sparks says.

Other students have benefited from work in Sparks’ lab as well. Last year, Sparks, Berberich, and Saul supervised two teams of senior biomedical and chemical engineering majors whose yearlong, self-directed capstone projects focused on the new 3-D printing platforms in development.

One of the two teams won a prestigious Undergraduate Research Award, which provides financial support for the university’s most promising faculty-mentored research by students. Sparks and Berberich plan to mentor two more teams this year.

“By involving students in research — where there is no recipe or cookbook that tells you, ‘If you follow all these steps, you will get the exact answer you’re expecting’ — I help student engineers develop not only technical skills, but also the problem-solving skills they’ll need to meet the growing demand for AM in the economy,” Sparks says.

Her commitment to mentoring may mean that her contributions to the field of AM will extend well beyond her own discoveries and innovations to influence those of future generations of engineers.

Written by Heather Beattey Johnston, Associate Director & Information Coordinator, Office for the Advancement of Research & Scholarship, Miami University.

Image of hand holding hydrogel by Heather Beattey Johnston, OARS. Image of Fitzgerald and Sparks by Jeff Sabo, Miami University.

This post originally appeared as an article in The Miamian, the magazine of Miami University’s alumni association.  It is re-used here with permission.

A graphic representation of the KCNQ1 protein. Two parallel corkscrew shapes are arranged on a black background. The shapes are rainbow colored.

Team lays groundwork for developing treatment of cardiac disorder

Four graduate students and a postdoctoral researcher pose with equipment they use to conduct research
Members of professor Gary Lorigan’s research team include (from left to right): graduate student Andrew Craig, postdoctoral researcher Dr. Indra Dev Sahu, and graduate students Lauren Bottorf, Dan Drew and Afu Zhang. Not pictured are graduate student Lishan Liu and undergraduate students Megan Dunagan, Raven Comer, Kunkun Wang, and Avnika Bali.

 

“Scared to death,” is more than a hyperbolic phrase to sufferers of long QT syndrome (LQTS); it’s a very real possibility. In LQTS, exercise and unexpected noise – like the ring of a doorbell or the backfire of a car engine – can set off potentially fatal heart arrhythmias in otherwise healthy children, teenagers, and young adults. It may even be a cause of sudden infant death syndrome (SIDS).

Most cases of LQTS are the result of inherited genetic mutations. But while scientists have identified a number of genes associated with LQTS, the mechanism by which mutations in these genes affect the electrical system that controls the heart’s rhythm is not well understood. As a result, the development of medical treatments for the disorder has been limited.

Gary Lorigan wants to change that. A professor in Miami’s Department of Chemistry & Biochemistry, Lorigan is working to describe the structural and dynamic properties of proteins produced by two genes implicated in LQTS: KCNE1 and KCNQ1.

Together, the KCNE1 and KCNQ1 proteins control the electrical potential of a cardiac cell by managing the flow of positively charged potassium ions across the cell’s membrane. “We know that the protein produced by KCNE1 binds to the protein produced by KCNQ1 to regulate the flow of potassium, but we don’t know how it binds or where it binds,” says Lorigan. “We know that mutations cause differences in this binding, but we don’t know why.”

In an effort to answer these questions, Lorigan and his colleagues – including a post-doctoral fellow, five graduate students, and seven undergraduate students – are using nuclear magnetic resonance (NMR) and an advanced electron paramagnetic resonance (EPR) technique known as double electron-electron resonance (DEER) to analyze how the KCNE1 and KCNQ1 proteins are built, how they move around, and how they bind.

In DEER, special molecules are used to tag specific regions within a protein or other macromolecule. Lorigan and his team use these so-called spin labels to measure distances within the KCNE1 and KCNQ1 proteins. “That’s how we’re actually able to visualize their structure,” he says.

One year into a project funded with $1.1 million from the National Institutes of Health (NIH), Lorigan’s team has managed to define the structure of the KNCE1 protein in the cell membrane. “That was our goal for the first year,” he says. “We just submitted the paper on that.”

The ultimate goal of the four-year project, according to Lorigan, is to “get structural information and relate that to function.”  Once that fundamental work is complete, the Lorigan team will have paved the way for translational scientists to begin developing new treatments for patients with LQTS and, potentially, other forms of arrhythmia as well.

Written by Heather Beattey Johnston, Associate Director & Information Coordinator, Office for the Advancement of Research & Scholarship, Miami University

Illustration by Pleiotrope (own work) [Public domain], via Wikimedia Commons. Photo courtesy of Gary Lorigan.