Margaret Lange

#IAmScience Billy Schulze

October 1, 2021 By Lauren Hines in #IAmScience Tags: virology

By Lauren Hines | Bond LSC

The best piece of advice Ph.D. candidate Billy Schulze ever received was from his father before a baseball game in high school. In past games, Schulze kept striking out. He wasn’t getting any runs. Things seemed bleak.

Schulze’s father pulled him aside and said with a smile, “Don’t suck.”

“That just kind of made me giggle,” Schulze said. “I think the real message behind that story is don’t think about it too hard. Relax. Have some fun…You can’t take things too seriously, having a sense of humor is so important. Working hard and pushing through problems is vital, especially in science where failure is so common.”

Schulze has brought that mentality to his research in the Margaret Lange lab at Bond Life Sciences Center since he joined in 2019. Whether he’s working on innate immunity or becoming one of the first biomedical engineer graduates at Mizzou, Schulze understands balance is vital in and out of research.

Taking after his father, Schulze wanted to become an engineer. However, it didn’t quite tick all his boxes.

“I have always been fascinated with biology,” Schulze said. “I just distinctly remember being in eighth grade when we went out to the pond water behind my middle school and looked at the pond water with a microscope. Seeing all of the protozoa and stuff that are in the pond water was really cool to me, and that just kind of stuck with me.”

Schulze merged engineering and biology when he became one of the first four students to graduate from biomedical engineering in 2018.

Soon after going back for his Ph.D., Schulze founded the Molecular Pathogenesis and Therapeutics Graduate Student Organization (MPTGSO). It’s aimed at improving the MPT degree by facilitating student feedback to faculty.

“I think that’s the thing I’m most proud of that I’ve done here, just being president of [MPTGSO], founding that and really just trying to be a voice for the entire student body of the program to the faculty in an attempt to just make everybody’s lives better within the program,” Schulze said.

When not helping graduate students, Schulze is in the Lange lab studying viruses, the innate immune systems and what causes Toll-like receptors (TLRs) to activate. TLRs are a class of receptors that can recognize various structures and molecules to trigger an immune system response. The Lange lab focuses on nucleic acid detecting TLRs.

Schulze is using a piece of the poliovirus genome (PV-5) known to bind to these specific receptors to create an immune response to the virus. This allows him to see which receptors activate and why.

“We’re asking what specifically is in PV-5 that is activating the receptor,” Schulze said. “So as opposed to looking at the receptor from the amino acids and what amino acids are required for binding, we’re looking at the RNA, and what RNA structures and motifs are required for binding to TLR.”

The Lange lab is creating a library of RNA sequences based on the genetic information of PV-5 to find which receptors activate.

“In this pandemic-affected world, viruses are at the forefront of health right now, and it’s something that everybody’s thinking about, and we’re specifically looking at the host-virus interface, something that is not necessarily the best understood,” Schulze said. “But at the same time, if we can help to modulate the immune response to viruses, we can potentially have better…potential antiviral therapeutics.”

When Schulze joined Bond LSC in 2016 as part of the Marc Johnson lab, he still had to learn all basic bench skills. Johnson lab supervisor Terri Lyddon was the one who showed him the ropes.

“He was definitely a worthwhile undergraduate student to have in the lab,” Lyddon said. “He was dependable, and he liked the work and came in with a positive attitude every day.”

Lyddon remembers how Schulze was always the one to speak up in lab meetings and ask questions about anything from the lab equipment to why they used particular procedures.

“There are certain levels of enthusiasm and inquisitiveness that come with almost anybody that comes to the lab because you have to want to do this kind of work in the first place…but he brought it to the lab in a unique way,” Lyddon said. “He was curious, and while some others may be curious, they don’t go on to find out the answers to those questions.”

When Schulze’s time in the lab eventually ends, he hopes to move on to a biotechnology company he truly believes in. For now, he’ll be in the lab keeping his dad’s advice in the back of his mind.

“Frankly, I think [science] is a frustrating field to work in, but it is also one of the most rewarding fields for that reason because you’ve overcome so much to find what you found, to prove what you’ve proven,” Schulze said. “I think it’s really cool, but it does require a lot of persistence.”

#IAmScience Margaret Lange

February 19, 2021 By Lauren Hines in #IAmScience Tags: vaccines, virology

By Lauren Hines | Bond LSC

Building a community through screens and limited interaction can be difficult. However, it’s no problem for Margaret Lange at Bond Life Sciences Center.

“I’ve met such wonderful people,” Lange said. “It really is true that if you surround yourself with the right kind of people who are positive, who think creatively and who ask good questions, it shows you how to model that behavior yourself. It teaches you to be better and helps you think better.”

Lange was originally part of the Donald Burke lab until she became an assistant professor of Molecular Microbiology and Immunology in the School of Medicine and established her own lab in Sept 2019, getting her start in Bond LSC lab space. Even though March 2020 brought shutdowns and restrictions, Lange still found herself in a mentoring role.

“I’ve had some mentoring experience but never as the primary investigator (P.I.) of the lab, so it’s a new experience for me,” Lange said. “I’m learning from that and learning from them and, hopefully, they’re learning some things from me as well.”

Lange understands that establishing a lab requires equipment and published papers, but also a good team.

“The reason I joined her [lab] is that women in science in a leadership role is very important and that needs to be encouraged,” said Rachna Aneja Arora, research scientist in the Lange lab. “I see her as a good leader and a good mentor. She has a very inspirational role and can be a role model for the young girls and women in science to take on the challenging role to be a P.I.”

However, Lange’s path towards science began before she even arrived at Mizzou.

Growing up in rural Missouri, Lange attended a small high school that didn’t offer many science classes beyond the traditional chemistry and anatomy classes.

“I didn’t even know at that time that you could do research in a lab,” Lange said. “I had no idea what opportunities were available.”

She did have some knowledge of microbiology since her mother was a medical technologist at the local hospital where she spent time identifying microbes that were causing infections in patients. So, Lange decided to enroll in a microbiology class once she started college. Not too long after, the professor asked Lange to help her with her research.

“If it wasn’t for her, I never would have probably tried doing research at all,” Lange said. “It’s really fun to design experiments and to answer questions. And so that was really kind of where my love for that started to show, or at least become evident to me, anyway.”

Since then, Lange has been interested in how cells can sense viruses and how that shapes immune signaling.

Humans have many receptors that can recognize different parts of viruses and can cause different immune responses based on what they’re recognizing.

“We really try to understand what is working at the level of the virus to shape those responses and how that influences how our immune system is able to fight those viruses,” Lange said.

The Lange lab is currently looking to improve the host-virus interaction regarding vaccines.

Vaccines generate a response that is specific to a certain component of a virus. However, just focusing on a single protein or nucleic acid is not enough to generate a robust and specific immune response. So, researchers like Lange are working towards improving adjuvants — immunostimulants in vaccines — to create a stronger response that helps shape antibody and T cell responses.

“Investigating what types of nucleic acid motifs can actually bind and signal through these pattern recognition receptors helps us design better adjuvants that can better shape the immune response for a specific pathogen,” Lange said. “For example, if you use a nucleic acid from the SARS coronavirus, it might shape the immune response in a specific way targeted to that specific virus, and then you hopefully get a better efficacy for your vaccine.”

For now, Lange and her team are working towards developing their lab and getting manuscripts underway.

“I really admire her for all she’s doing,” Aneja Arora said. “I think we will work harder to get things moving forward. So, I just wish her all the best and wish her good luck setting up a very established lab.”

Homegrown researcher

October 16, 2019 By Mariah Cox in Research Tags: Mizzou Research

Years at MU lands student turned faculty tenure-track position

Maggie Lange-Osborn is a newly appointed assistant professor in the Department of Molecular Microbiology and Immunology. | Photo by Roger Meissen, Bond LSC

By Mariah Cox | Bond LSC

Where can passion, hard work and more than a decade worth of experience get you? They landed Maggie Lange-Osborn her own research lab on the University of Missouri campus.

Lange is starting down that path in Bond Life Sciences Center but will move to a permanent space in either the Medical Science Building or Schweitzer Hall eventually. She’s excited to spread her wings and establish herself independently of her past role in the Bond LSC.

In the meantime, she’s working arduously to build her lab from the ground up. From small materials such as plastics for cell culture, pipettes and pipette tips and chemicals to make buffers to large expensive equipment, Lange will eventually need it all.

“Walking into the lab, you don’t realize all of the things you need to do an experiment. When I walk into my lab space, I literally have nothing,” said Lange, a newly appointed assistant professor in the Department of Molecular Microbiology and Immunology (MMI). “You have to think about all of those things, you know it’s not just the equipment it’s the pipettes, the incubators, the hoods and then also the materials to put in those things.”

Luckily with 10 plus years in the building, Lange knows of all of the shared resources available to her, so she doesn’t have to invest in many expensive machines just yet.

“I cannot wait to do my first experiment with my own equipment,” Lange said.

Lange began her career at MU in 2003 as a Ph.D. student in the Molecular Microbiology and Immunology and Veterinary Pathobiology Graduate Program, whether she knew it at the time or not.

When applying for faculty positions, Lange worried that she would be placed in a box, unable to separate herself from her graduate work if she stayed at MU. With time, she’s found that hasn’t been the case.

“Even though I’ve been here for so long, I’ve been able to surround myself with people who know more than me and who have different areas of expertise than I do,” Lange said. “I can still branch off and learn a lot from other researchers, which is what I found really attractive about Mizzou.”

Her segway into research occurred during her first year as a graduate student in an MMI lab in the School of Medicine. Under Michael Misfeldt at the School of Medicine, Lange studied pattern recognition receptors in the innate immune system, which is the body’s first line of defense against a virus or bacteria.

The specific receptor she worked with recognizes a component of viruses. From there, Lange wanted to understand how a host is able to respond.

“After working on that I felt like I had a really good grasp of the host response side and I wanted to get more of the virus side to understand virus replication and what types of replication mechanisms work to signal the host from that perspective,” Lange said.

That led Lange to join Bond LSC in 2008 as a post-doctoral researcher in Donald Burke’s lab. Known for specializing in HIV research and viral biology, the Burke lab gave Lange the opportunity to understand virus side interactions.

Lange wasn’t quite ready to move on at the end of her post-doc, and the success with her research led Burke to invite her to stay on as an assistant research professor.

“During that time, I was more exposed to leading people and mentoring people in the lab. I was able to get some teaching experience in that role as well in the infection, immunity and advanced virology classes,” Lange said. “The position evolved into really enjoying all of the components that would be required for a tenure track position and it grew from there.”

In her sixth year as an assistant researcher, Lange decided she was ready to run her own lab. However, she knew it would be a challenge to secure a faculty position and even more difficult to stay at MU.

But, her experience in the Burke lab and her proven ability to obtain grant funding worked in her favor.

“It’s really nice to stay in Missouri because mine and my husband’s family are here,” Lange said. “When I was growing up, my dad was in the military and we moved around a lot, so I never got to know my grandparents or cousins. It’s really nice now that my kids get to have those relationships with their extended family.”

Her goal with her new lab is to combine her knowledge of viral interaction in the body and hosts’ response to infection.

Three projects currently in the works for grant submission focus on host-virus interactions and how different host factors and viral proteins interact during replication. One specific project looks at the host factors that are involved in HIV induced death caused by different HIV proteins.

“While HIV has been around for a long time, there are still things we don’t know about it. With the research, I’m getting back to my innate immunity roots and looking at exactly how viruses interact with innate immune receptors and signaling pathways and how that interaction dictates pathogenic outcomes,” Lange said.

Understanding the death pathways for HIV can lead to the development of a strategy to preserve T cells and facilitate the death of the virus. Additionally, it can lead to the development of therapies toward eradication.

Her excitement isn’t just for her new lab, it’s also for her newfound opportunity to provide students with lab experience and open up the possibility of research for those who haven’t had access to it.

“I’m from a rural community and I didn’t even know that a Ph.D. existed when I was in high school,” Lange said. “I’d really like to present those opportunities to people like me who have no idea that they’re even available. There are so many things you don’t realize are possible because of the environment that you’re in whether it be in rural or inner-city communities.”

While unknowingly launching her career at the outset of her Ph.D. program, Lange is grateful her path led her here.

“It’s been really fortunate for me, the way the whole process developed. I love this building and the awesome people I’ve met here, but I’ve been here since 2008, so having a fresh perspective elsewhere could be beneficial. I’ve worked a long time with both Marc Johnson and Donald Burke and being away from the building will allow me to meet new investigators and establish new collaborations,” Lange said. “While we still have very productive collaborations and have promising, active projects, it will help demonstrate that I’m separate from them and have my own interests as well.”