Biomedical Research Series: Dr. Michael Butcher

Within the Department of Biological Sciences at Youngstown State University, there are many areas of research being explored by faculty and students alike. In a monthly series, we will highlight faculty research that covers various aspects of biomedical efforts from DNA to bacteria, fungi, and more.

Dr. Michael Butcher is an Associate Professor of Biological Sciences at YSU. He earned his PhD in Zoology from the University of Calgary. Afterward, he completed a two-year NSF post-doctoral fellowship at Clemson University before becoming a full-time professor at YSU.

At YSU, Dr. Butcher conducts three different types of research with assistance from multiple graduate and undergraduate students. The main focuses of his laboratory research are the mechanical properties and shape of limb bones, fiber architecture and force production in the limb muscles, and development of muscle fiber types. His most recent work involves studies of muscle form and contraction activity in tree sloths.

Every other year, Dr. Butcher has traveled to The Sloth Sanctuary in Limón, Costa Rica. This gives him the opportunity to study species of two-toed and three-toed sloths.

On his most recent trip, he and his research team visualized live muscle contractions of the sloths using implanted fine wire electrodes. They recorded muscle activity while sloths performed combinations of walking, climbing, and hanging exercises. In addition, Dr. Butcher and his team conducted very detailed dissections on cadaver sloths to learn about their muscle architecture.

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“What we do is take geometric measurements of the muscles,” Butcher said. “For example, how long is the muscle belly, how long are the muscle fibers, at what angle are the muscle fibers? Then we apply a couple basic calculations.”

They could then estimate the force, power, and torque (strength) properties of sloth muscles. Dr. Butcher considers this approach to the study of muscle form and function “simple, but elegant.”

To understand his research interests, it is important to know some of the unusual characteristics of a sloth.

“Why a sloth?” Dr. Butcher was asked. “Because they’re old and interesting mammals that do something really different from what humans are capable of doing.”

In a sloth’s body, there is only about 24% muscle mass. Dr. Butcher and his students are finding that their muscles have a high tolerance for lactic acid and rarely fatigue, unlike skeletal muscles in humans. Much to his surprise, Dr. Butcher is also learning that sloths primarily use anaerobic mechanisms to allow them to conserve energy and resist fatigue. This contributes to a sloth’s ability to hang from tree limbs for extended periods of time.

Other factors that relate to the strength and stamina of sloths are lower body temperature, lower metabolism, and slower digestion than most placental mammals.

“Sloths also have a network of blood vessels in their forearms that lowers the temperature of the muscles,” Butcher said. “This allows the muscles to remain strongly contracted for gripping branches while using energy at a slower rate.”

With these distinctive characteristics, sloths can conserve a tremendous amount of energy. For this very reason, Dr. Butcher finds sloth research remarkably insightful.

Dr. Butcher does not simply perform research to learn more about muscle structure-function in sloths, but rather to give further evidence of the performance range of muscles, in general. He wants to continue studying how muscles are put together and how they work, as functionality is diverse for animals depending on their lifestyle.

While this research has medical applications such as bioengineering artificial muscles and limbs, Dr. Butcher remains committed to fundamental science where his findings contribute towards education in the scientific community, future textbooks, and enhancement of the courses that he teaches at YSU.

Dr. Butcher stresses the immense contribution from his students. He believes that they are vital to his research efforts. To further his studies in primitive mammals Dr. Butcher plans to travel to Argentina this fall to investigate muscle properties in rare species of armadillos.

Biomedical Research Series: Dr. Gary Walker

Within the Department of Biological Sciences at Youngstown State University there are many areas of research being explored by faculty and students alike. In a new monthly series, we will highlight faculty research that covers various aspects of biomedical efforts from DNA to bacteria, fungi, and more.

Dr. Gary Walker is a professor and chairperson of Biological Sciences at YSU. He obtained a PhD in Biological Sciences from the Wayne State University of Michigan. He began graduate school with an interest in becoming a developmental biologist with focus on cell division and later in stem cells.

His interest in biomedical research began decades ago but recently changed direction when he collaborated with a local neurologist, Dr. Carl Ansevin. They wrote several papers together and heavily researched muscle proteins. Now he is mainly focusing on the basic molecular programming of muscle tissue with anticipation that he can eventually engineer a functional muscle.

Dr. Walker is currently studying the growth of muscle cell cultures to advance the fundamental understanding of muscle development and function. In addition, he is interested in tissue engineering, specifically 3D-printed structures, which will be used primarily for therapy purposes.

Given his research background, one of his goals is to create functional muscles. To create a 3D-printed tissue structure, Dr. Walker grows myoblasts in cell cultures that are then mixed with a bio gel. The bio gel aides in the suspension of the cells and maintains the 3D structure throughout the printing process. A computerized 3D fluid printer is then used to create a specific geometric structure allowing the “tissues” to transfer to culture vessels so that the myoblasts can grow.

“As you can see, these myofibers form in all sorts of directions,” said Dr. Walker. “So you can’t make a functional muscle because in a functional muscle all these fibers have to be aligned parallel.”

In the end, once the cells are understood and a live tissue is formed, Dr. Walker wants to tinker with the geometry of the tissue, making it more like a standard muscle tissue.

Once the structure is fit for usage in medical procedures, his personal hope for the 3D-printed muscle tissue is to benefit trauma patients and those who experience muscle diseases. This research project has tied together his love of growing cells and researching how functional tissues are formed. The project is also a great way to show the transition between basic and applied knowledge.

There is great potential for this research and Dr. Walker could be an important part of this advancement of biomedical technology.

Recent Publication: Biology Student, Faculty, and Staff

Thomas DR, Chadwell BA, Walker GR, Budde JE, Vandeberg JL, Butcher MT. “Ontogeny of myosin isoform expression and prehensile function in the tail of the gray short-tailed opossum (Monodelphis domestica),” Journal of Applied Physiology, May 2017. DOI: 10.1152/japplphysiol.00651.2016

Former YSU biology student Dylan Thomas authored this paper in collaboration with faculty and staff from YSU, Ohio University, and the University of Texas Rio Grande Valley. The paper was submitted in July 2016 and was accepted and published in May 2017 by the American Physiological Society.

Abstract:

Terrestrial opossums use their semi-prehensile tail for grasping nesting materials as opposed to arboreal maneuvering. We relate the development of this adaptive behavior with ontogenetic changes in myosin heavy chain (MHC) isoform expression from 21 days to adulthood. Monodelphis domestica is expected to demonstrate a progressive ability to flex the distal tail up to age 7 months, when it should exhibit routine nest construction. We hypothesize that juvenile stages (3-7 months) will be characterized by retention of the neonatal isoform (MHC-Neo), along with predominant expression of fast MHC-2X and 2B, which will transition into greater MHC-1β and 2A isoform content as development progresses. This hypothesis was tested using Q-PCR to quantify and compare gene expression of each isoform to its protein content determined by gel electrophoresis and densitometry. These data were correlated with nesting activity in an age-matched sample of each age group studied. Shifts in regulation of MHC gene transcripts matched well with isoform expression. Notably, mRNA for MHC-Neo and 2B decrease, resulting in little-to-no isoform translation after age 7 months, whereas mRNA for MHC-1β and 2A increase, and this corresponds with subtle increases in content for these isoforms into late adulthood. Despite the tail remaining intrinsically fast-contracting, a critical growth period for isoform transition is observed between 7 and 13 months, correlating primarily with use of the tail during nesting activities. Functional transitions in MHC isoforms and fiber type properties may be associated with muscle ‘tuning’ repetitive nest remodeling tasks requiring sustained contractions of the caudal flexors.

Recent Publication: Biology Faculty & Students

STEM faculty members on the paper: Xiangjia “Jack” Min, Feng Yu, Chester Cooper
STEM graduate students:  Brian Powell, Vamshi Amerishetty, John Meinken
STEM undergraduate student: Geneva Knott

Powell B., Amerishetty V., Meinken J., Knott G., Feng Y., Cooper C., and Min X.J., 2016, “ProtSecKB: the protist secretome and subcellular proteome knowledgebase,” Computational Molecular Biolog 6(4): 1-12.

Abstract:

Kingdom Protista contains a large group of eukaryotic organisms with diverse lifestyles. We developed the Protist Secretome and Subcellular Proteome Knowledgebase (ProtSecKB) to host information of curated and predicted subcellular locations of all protist proteins. The protist protein sequences were retrieved from UniProtKB, consisting of 1.97 million entries generated from 7,024 species with 101 species including 127 organisms having complete proteomes. The protein subcellular locations were based on curated information and predictions using a set of well evaluated computational tools.  The database can be searched using several different types of identifiers, gene names or keyword(s). Secretomes and other subcellular proteomes can be searched or downloaded. BLAST searching against the complete set of protist proteins or secretomes is available.  Protein family analysis of secretomes from representing protist species, including Dictyostelium discoideum, Phytophthora infestans, and Trypanosoma cruzi, showed that species with different lifestyles had drastic differences of protein families in their secretomes, which may determine their lifestyles. The database provides an important resource for the protist and biomedical research community. The database is available at http://bioinformatics.ysu.edu/secretomes/protist/index.php.

Faculty Research: Dr. Caguiat

Dr. CaguiatDr. Jonathan Caguiat, an associate professor in the Department of Biological Sciences at Youngstown State University, can trace his research on metal-resistant bacteria back to his time spent as a graduate student at Michigan State University.

He explained the history of the Y-12 plant in Oakridge, TN, and how toxic metals like uranium and mercury contaminated the soil and water there during World War II and the Cold War.

“My PhD advisor went down to Oakridge in 1989 and he dug up some soil samples right next to the plant and then a mile downstream,” said Dr. Caguiat. “So I work with bacteria that has been isolated from this creek. I look at different metal resistances.”

After his PhD advisor brought back the samples, Dr. Caguiat added a growth medium and spread the samples on plates. He froze the bacteria that grew to preserve them for later study.

“So we’ll expose them to different types of metal like mercury, maybe cadmium or zinc, looking for genes that are involved in [metal resistance],” said Dr. Caguiat. “We have isolated some bacterial metal resistance genes and can search for them in other bacterial strains.”

Some of the practical outcomes of this research are bioremediation—“cleaning up” in nature—and human medicine. Different metal resistances have different applications, and much of this is still being studied.

Dr. Caguiat earned his bachelor’s degree in biology with a concentration in molecular biology, and his PhD is in microbiology.

He uses his research as a valuable classroom tool to get students working hands-on and prepared for their own future research.

Improving DNA Research on Campus

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The Molecular Biology Analytical Core Laboratory, located in Ward Beecher 4050, is a DNA sequencing facility run by Molecular Biology Specialist Ed Budde.

Until recently, the equipment in the lab was scattered around in different locations. It was brought together in this singular location to provide all of the resources in a common area.

“This room used to be a teaching lab that was used for service courses,” said Biology Chair Dr. Walker. “When we sort of changed the curriculum a bit, this became available.”

Ed Budde works in the lab full time and is trained on all of the equipment and software.

“Usually what I do over here is I support the research of the faculty members and the graduate students, and undergraduates as well because a lot of them are learning how to do things like extract DNA and purify DNA,” said Budde.

Recent projects utilizing the lab are Dr. Cooper’s work studying the genetic makeup of disease-causing fungi and Dr. Caguiat’s research involving metal resistance genes.

Some of the capabilities of the lab are gene sequencing and quantitative PCR, which are available to any students, faculty, or partners of the university.

“We’re trying to market this to outside interests that don’t know this exists,” said Dr. Walker.

The lab is a vital resource in the department that supports research at the undergraduate and graduate levels.

For more information about the lab, the technology, or available services, stop in and talk to Ed Budde or contact Dr. Walker at grwalker@ysu.edu.

Department of Biological Sciences Demonstrates MAKO Technology

The Youngstown State University Department of Biological Sciences partnered with Stryker Orthopaedics to demonstrate and certify two physicians on the use of Stryker’s MAKO Surgical Robotic Arm Interactive Orthopaedic technology.

Stryker used the Biology anatomy lab on Oct. 23 to demonstrate this technology by having the two surgeons perform hip joint replacement surgeries on a cadaver. Students were welcome to watch the demonstration and ask questions.

Dr. Raymond Duffet,  an orthopaedic surgeon and team physician for YSU Athletics, who was certified in the use of the new technology at the demonstration, said the MAKO technology uses set points to outline the margins and depth of the acetabulum, which is the “cup” on the hipbone that forms the socket portion of the ball-and-socket hip joint..

“In other words, we almost take a 3D picture of the cup … all around it, and then depth because we don’t want to go too deep,” Duffet said. “After that, then the computer tells the reamer how to ream it to achieve that perfect result, [which results in a] perfect, accurate match.”

The reamer is a half-ball shaped grinder head at the end of a drill that is used to grind the acetabulum into the shape needed to fit the prosthetic joint. During the surgery, the head of the femur bone is cut off, hammering the femoral part of the prosthesis into the cut end of the femur, and attaching the ball to the femoral prosthesis. The hip joint is then put back together.

Duffet said that in the United States between 400,000 and 500,000 total hip joint replacement surgeries are performed every year. With technology like MAKO, hip replacements will be able to be fitted more perfectly, decreasing the likelihood of having to get additional hip replacements down the road.

Dr. David Weimer was also certified to use MAKO during the Oct. 23 demonstration. He said that the technology allows for accurate information in real time, which leads to consistency from case to case.

“Everyone’s anatomy is a little different,” he said. “This helps you match their anatomy.”

Weimer also said that he thinks the technology will catch on.

“I think this is going to continue to grow in popularity,” Weimer said. “I think more and more cases will be done with robotic assistance. Originally this started with prostate surgery and now it’s application has expanded into orthopaedics. I think more and more surgeons will come on board with this type of technology.”

MAKO technology has already been used to perform nine hip replacements at Northside Hospital.