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Zooming in on the tools: TS33 Secretion System

Salmonella is one bacterium everyone’s heard of. It’s the scourge of meatpacking plants and involved in spinach recalls every year, causing unwelcome intestinal unrest and dangerous disease when encountered in high enough numbers.

William Picking wants to better understand how to combat this and other food and water system hazards. The Bond Life Sciences Center scientist reached down to take a piece of paper to quickly jot down a drawing of a nifty way some bacteria have evolved to avoid the defenses of the animal cells it infects. One of the focuses of his research is to determine how the bacterial type 3 secretion works. Understanding this secretion apparatus may help scientists create better, more targeted drugs to fight pesky bacterial infections and outbreaks.

His drawing showed the type 3 secretion apparatus (T3SS), the bacterial structure that injects specialized proteins into cells to avoid being detected and attacked by those cells. In some cases, the apparatus actually invades those cells so the bacteria can grow inside them. Scientists like Picking aim to use proteins from this needle-like structure to develop new strategies to prevent disease

This “injectosome” is basically a syringe.  Composed of a base with a channel through it connected to a needle, this apparatus injects into and through the membrane of its host cell to get its proteins inside.

Scientists have a general idea of what the T3SS secretion apparatus looks like, but Picking’s current research focuses on understanding exactly how the injectosome works as a microscopic machine at a deeper level.

Picking and his team zoom in on the specific way that it selects the proteins to be secreted and energizes that process so they can deliver their specialized proteins.

This process must be coordinated so that the proteins are properly injected into the cell, so they invade those cells or, in some cases, kill the host cells trying to harm the bacteria.

The power behind this process comes from the ability of bacteria to recognize the surface of the organism to form a hole in the host cell membrane. The needle then passes those proteins through the hole.

The parts of the injectosome that are inside the bacteria are involved in determining what proteins are secreted and in what order.  This overall internal segment is called the sorting platform and it also provides the actual power that drives the secretion process, causing the secreted protein to be unfolded and then forcing it through the needle and ultimately into the host cell. It makes the injection of this process easier and speeds it up.

“We have a general idea of what the sorting platform looks like but our research focuses on improving our understanding of this structure to get at the mechanisms guiding secretion,” Picking said. “We even want to understand the movements within this structure that are part of the secretion process. “

Picking’s main focuses are bacteria like Salmonella and Shigella, but other bacteria like Pseudomonas aeruginosa can shut down the communication some immune system cells use to combat an attacking microbe.

“By understanding this apparatus at a high resolution, at a detailed structural level, we can potentially design drugs to inhibit the process of infection.” Picking said.

The trick is to reverse engineer a drug that operates like an antibiotic from the knowledge of T33s. That small drug could block the process of infection, and the body’s immune system can kill off the invader.

The problem that arises for scientists is the antibiotic often kills the bacteria. This leads to antibiotic resistance, a process called selective pressure.  That’s not good news. The drug engineered from reverse T33s shuts off the bacteria instead of killing it.  But, by shutting off the bacteria, your immune system will naturally recognize the pathogen or foreign invader and then destroy it itself. This is an ingenious idea, gaining popularity with bacterial scientists meant to avoid the often-inevitable bacterial resistance.

Bacterial resistance is a chronic problem in our world where antibiotics become less effective as the bacteria evolve around its protection. This causes problems the problems you hear in hospital systems where MRSA bacteria threaten life after antibiotics fail to fight them off or even how low levels of antibacterial agents in hand soap create more persistent colonies on surfaces.

Zooming in on the T3SS injectosome may give clues to better fight infection and reduce the number of people affected by dysentery and other common bacterial infections.

“It’s a great goal, not a goal our laboratory will accomplish in the immediate future, but we hope to provide the information for someone else to create these drugs to get around the problems of antibiotic resistance.” Picking said.

By Beni Adelstein | Bond LSC

Research skills aren’t built in a day, but Cynthia Tang’s diligence brought those skills to bear as she recently received a National Institutes of Health fellowship to further her budding career in science.

“Receiving the F30 fellowship means that the NIH sees value in my research proposal, in my training environment at the University of Missouri, and in my potential to become an independent physician-scientist,” said Tang, who works in Henry Wan’s lab at Bond Life Sciences Center. ­

This F30 predoctoral fellowship supports the research of students pursuing M.D.-Ph.D.’s. These awards help lighten the financial burden of a degree path that takes the better part of a decade for Tang and others pursuing their passions in research.

Tang came to the University of Missouri in 2018, started her journey as an M.D. student, then took a break to pursue her Ph.D. In the dual M.D.-Ph.D., the first two years are spent in pre-clinical studies followed by a full-time Ph.D. for three to five years and then students finish up with clinical training.

So, what project captured NIH’s attention?

Tang focused on how Covid-19 spreads and who gets it in rural areas. The aim is to identify people who have a higher chance of getting sick or being hospitalized so preventive measures can be offered earlier.

Lots of data must be gathered to accomplish this. Scientists sequence the genome of coronavirus variants­ to get a detailed profile and compare how that genetic makeup evolves over time. They do this by testing nasopharyngeal swabs—the Q-tips that are commonly used for covid tests—of people suspected of coronavirus infection. They use electronic health records to see who is getting sick, and add demographic information on age and location to the clues researchers analyze.

Tang focuses on rural populations in the U.S., especially in Missouri, because there is a gap in data from those communities. Once those at highest risk are identified, scientists can prioritize early prevention of COVID-19.

“Our biggest motivation for studying rural populations is so that we can better understand the way the virus changes and how to better serve those communities,” she said.

The process of planning for the grant itself enabled Tang to finetune the quality of her work.

“I feel like it helped speed up my Ph.D.,” she said. “We had to break down the research study into all the little pieces of what needs to be done and what to do when things go wrong. Everything must be so well thought out to put the grant together.”

After Tang’s initial fellowship application was rejected, she challenged herself to put together a completely new study design in under two months for her second proposal.

“It was the best thing that ever happened” said Tang, smiling. “I am extremely grateful to Dr. Wan and my thesis committee.”

This fellowship has provided many opportunities to Tang. She traveled overseas to present her findings at international conferences, which connected Bond LSC research with an international science community. Last year she was in Belfast, Ireland, and this month she will be in Valencia, Spain.

Where is Tang now?

She’s working remotely as she wraps up her Ph.D. and will graduate from Mizzou this upcoming December. Once she secures that Ph.D., she will head out to the University of North Carolina at Chapel Hill in January 2023 to finish her clinical training. Then she will enter the homestretch of her dual degree journey, finishing her M.D. in May of 2026.

Cynthia Tang currently serves as president-elect of the American Physician Scientists Association and will continue in this role next spring.

Tang was recently first author on “SARS-CoV-2 and influenza co-infection: A cross-sectional study in central Missouri during the 2021-2022 influenza season.” in the Journal of Virology in 2022.

By Sarah Kiefer

The spikes that protrude from SARS-CoV-2 present a topography of peaks that drive one MU researcher to ask more questions.

To Kamal Singh, a principal investigator at Bond Life Sciences Center, assistant professor in the MU College of Veterinary Medicine, and the director of the Molecular Interactions Core those spikes are a changing map with every new variant of coronavirus, and they lead his lab to study its constant evolution of mutations and proteins.

The Singh lab recently found an unexpectedly high number of APOBEC-mediated mutations among a patient cohort from South India, who were vaccinated and have taken remdesivir  to treat COVID-19. Using data from patients from South India, Saathvik Kannan, a senior at Hickman High School and a computer programmer and researcher for the Singh lab, tracked changes to the virus’ proteins.

“Viruses are known to evolve under pressure, so what’s happening in this case is that antibodies recognize the virus in a cell, and the virus sees that, ‘okay, there is someone to stop me,’ so it makes mutations,” Sing said.

The virus’ genome often alters, by mutating, inserting, or deleting the building blocks within RNA and DNA known as nucleotides, depending upon the pressure that viruses experience. Only some of these sugar-containing nucleotides are mutated, but these small changes can form a new virus variant.

“A few months ago, we didn’t know the reason behind all of these different mutations in patients because we did not look for APOBEC-mediated changes in viral genome,” Singh said.

Kannan found that between October 2022 to January 2023, the mutations among the patient cohort varied between 114 to 83. With that information, he identified 50% of patients who have diabetes and that when they take insulin the APOBEC protein is also induced. This new discovery leads to more questions about those with underlying conditions like diabetes or hypertension, and how they are affected differently by the drug.

“Ideally if a virus were to evolve you would see a linear progression, but you don’t see that here,” Kannan said. “This shows us that APOBEC proteins are likely one of the causes of this evolution in the virus and the makers of these variants.”

When the number of mutations vary significantly, like in the cohort, it re-affirms that the COVID-19 variants evolve independently.

Viruses don’t stop to wait for researchers to find the root of the problem. They constantly change, and in cases where the patients are vaccinated and take remdesivir, the virus evolves by taking advantage of the APOBEC protein.

Singh started down this path of research early on in the pandemic. Through PCR tests — which converts tiny amounts of RNA into DNA then copies it to a measurable level — he learned more about each mutation by comparing new samples to the original viral strain. Until this point, there had only been around 40 identified mutations in the spike protein in the different XBB sub-variant, but Singh’s lab has identified two more. The details have been recently published in The Lancet Journal. The two mutations found in this process, A27S and T747I, were unique to this cohort.

“For the first time we’re able to get more clues on what is actually happening because we were able to compare it to patient samples in the XBB subvariant and we had a wealth of data to work with,” Kannan said.

The Omicron variant yields new mutations constantly — currently at 43 and counting — and presents plenty of opportunity to look for differences. Singh directs his team to comb through variant sequences to identify differences in their genetic code. Soon they begin to identify trends from one month to another.

“The main difference here was that we have high quality patient data this time, from a patient cohort in Southern India, as opposed to getting it from a database,” Singh said. “The patient cohort tells us that the mutations are more than what was reported before.”

From January to June of 2020, Kannan found mutations that were present in one hundred percent of the sequences. When the Alpha Beta variant arrived in November 2020, they immediately knew what the mutated changes were. Their findings were published in the paper, ‘Clinical characteristics and novel mutations of omicron subvariant XBB in Tamil Nadu, India – a cohort study,’ in April 2023 in the Lancet Regional Health – Southeast Asia Journal.

After new variants — such as the XBB sub-variant of Omicron — materialized, Singh’s lab identified existing drugs and new drug compounds that match structural weaknesses presented by mutations.

One way Singh’s lab keeps abreast of new variants is by utilizing the tools they have available to their advantage with in-house programs either in Python or in R programming languages. Their lab can construct non-infectious, virus-like particles that contain all the same characteristics as the virus minus its genome, or its genetic material makeup.

A collaboration between University of Missouri and University of Nebraska Medical Center helped identify the new drug compound, MU-UNMC-2 in addition to the MU-UNMC-1, previously found in late 2021, as potential coronavirus treatments.

Remdesivir, ribavirin, favipiravir, and molnupiravir were among existing drugs that can be used to treat COVID-19 under certain conditions. Remdesivir — previously ineffective as an Ebola virus treatment — initially proved somewhat useful for COVID-19. Molnupavir only showed moderate promise, and the two drugs were approved for emergency use by the FDA for the treatment of COVID-19. Remdesivir now has full FDA approval.

“To address the problem, you have to find the problem. Where is the virus? What can we address? And then we go after it,” Singh said. “My lab was the first one in the world who suggested when the pandemic came that these are a few drugs that can be used and remdesivir was one of them. I’m very proud that I could contribute to human health in that way.”

With knowledge of this new protein in hand, Singh’s lab now is moving forward to focus most of their attention on the APOBEC protein mediated mutations and how underlying health conditions can affect an individual’s reaction to certain drug compounds.

“The virus has been outsmarting us, outfoxing us, until now. As soon as we get something, it changes itself,” Singh said. “That keeps us motivated as we chase it.”

The Singh lab’s research on the XBB sub-variant mutations was published in the paper ‘Omicron SARS-CoV-2 variant: Unique features and their impact on pre-existing anitbodies’ in the “Computational and Structural Biotechnology Journal” in June 2021 and their updated findings can be found in the paper ‘Clinical characteristics and novel mutations of omicron subvariant XBB in Tamil Nadu, India – a cohort study,’ published in “The Lancet Regional Health – Southeast Asia Journal” in April 2023.

Funding provided by: Bond LSC, Swedish research Council, American Lung Association, National Institute of Dental and Craniofacial Research in collaboration with Prof. Gary Weisman of the Bond Life Sciences center.

By Beni Adelstein | Bond Life Sciences Center

Brian Thomas got the official letter in the mail Monday after months of waiting.

“It’s a long time coming,” he said, “lots of patience and collaboration.”

Thomas is one of two student scientists at Bond Life Sciences Center to receive F30 fellowships — officially the Ruth L. Kirschstein National Research Service Award (NRSA) — from the National Institutes of Health (NIH) this year, a first for MU.

The agency awards F30 fellowships to MD-Ph.D. students pursuing related areas as they work towards their doctoral degrees. Those awards add up, with up to six years of funding to cover costs of research and clinical training.

When Thomas originally applied, his proposal was rejected, but the second time was the charm. He studies cancer immunology in the lab of Donald Burke at Bond LSC.

“You learn from failure, reflect on it and grow,” he said. “You learn to think critically about your research proposal and organization.”

Cynthia Tang — also working toward her MD-Ph.D. dual degree — got official word about her award ahead of Thomas. It allows her to continue her research in the lab of Henry Wan at Bond LSC. She researches the evolution and spread of Sars-Cov2 — the cause of the Covid-19 pandemic. Her proposal was also rejected the first time, yet she persevered. She encourages other students to apply for the fellowship.

“You should really go for it. It seems like a lot, and it can be really intimidating when you look at the checklist and all the components,” Tang said. “But it is possible, and it is doable.”

Both students are thankful for what the fellowship has done for them. It pushed them to navigate the highly competitive grant application process as well as clearly outline their goals and ambitions.

“We have an incredible grants team and our faculty is amazing,” Tang said. “There are so many resources available at Mizzou.”

Thomas agrees.

“We have fantastic directors doing a wonderful job growing the environment of our programs and tending to our student’s needs,” he said.

This NIH fellowship is an opportunity for students to pursue their passions in science and research while alleviating financial burdens, giving researchers like Tang and Thomas the tools to succeed.

The Tom and Anne Smith MD-Ph.D. Program at the MU School of Medicine is a seven- to nine-year course of study that combines the traditional four years of medical school with the three to five years typically required to earn a doctorate in a scientific discipline. It prepares students for a career in academic medicine.

About Bond LSC
At Bond Life Sciences Center, the best answers come from working together. Our building and culture leverage expertise of faculty investigators to develop discoveries that matter. Our researchers represent diverse academic backgrounds with projects focused on infectious diseases, agriculture, informatics, the environment and other areas. By moving beyond the boundaries of departments, our research increases its impact and lays the groundwork for a better world while teaching the next generation of scientists.

By Sarah Kiefer | Bond LSC

Some of the most fascinating things in science happen at the border where one organism interacts with its environment.

That’s the case with root border cells, and Clayton Kranawetter is one individual exploring this frontier.

Kranawetter recently received a $223,000, two-year USDA National Institutes of Food and Agriculture Postdoctoral Research fellowship for his project on this group of cells. This fellowship is a part of a larger $12 million investment in multiple institutions by the USDA to expand research in the area of agricultural microbiomes. The University of Missouri is among 17 research institutions to receive funding.

“I’m still shocked by receiving the award. I was already having a good day when I received my award notice. I found a good parking spot in the garage and a quarter on the sidewalk, but then I got the email” said the postdoctoral fellow in the Lloyd Sumner lab at Bond Life Sciences Center. “I thought it was a mistake at first and then I realized, ‘oh, this is real.’”

This fellowship will sustain his work in an influential way as he dives into the secreted metabolites and mechanisms of isolated border cells and their impact on rhizosphere dynamics.

Metabolites are small molecules made or used when a cell breaks down food, reacts to certain signals or completes other essential processes. Some metabolites, such as glucose, are part of an organism’s central or primary metabolism and its basic life functions. Other metabolites, such as secondary or specialized metabolites, are less essential to sustaining life but no less integral as they help with plant defense responses. Identifying these metabolites can help researchers predict how plants will react to various biotic and abiotic conditions, such as high light, stress from salt, symbiotic interactions, and defense against pathogens.

“I love science because everything is a puzzle,” Kranawetter said. “Sometimes the puzzle is a struggle to put together and can look quite different from what you expected, but after everything is complete, it is always rewarding and empowering to see how the pieces fit together.”

Kranawetter’s work focuses on root border cells, which are vital to plant root health. These cells arise from the root epidermis, where the cell wall breaks down and the cells are physically released from the root but still surround the root tips. Border cells are held in place through a water-soluble, complex secreted matrix consisting of a polysaccharide mucilage, comprised of DNA, proteins, and metabolites. As their encasing material is water soluble, upon contact with water they wash away but are rapidly replaced within 24 hours after their removal. After border cells separate from the root tip, Kranawetter conducts large scale genetic reprogramming to divert most of their resources to secretion and specialized metabolism. In doing so, they serve a protective role against infection and environmental stress, but the scope of their functions is far from fully explored.

“Border cells are still very niche, and we don’t fully understand how they’re contributing yet, but we’re starting to see that they are more major players in the rhizosphere than we thought initially,” Kranawetter said.

Root border cells appear across most plant species. They are known influencers of dynamics within the rhizosphere — the layer of soil that is in direct contact with root secretions — but there are still a large number of unknowns about them.

Kranawetter’s previous work dealt with metabolites, or small molecules, and their differential accumulation in root tissues. He collected root border cells and separated individual root tissue types to create a metabolite atlas based on the Arabidopsis eFP browser – a computer program that shows the relative intensity of metabolites by tissue type in a heatmap context. This project builds on his work to further identify the molecules border cells secrete and how they mediate plant-microbe interactions.

Although this project does not directly correlate with his current research in the Sumner lab focused on differential metabolite accumulation in cultivated elderberry plants, it will allow Kranawetter to stay in plant tissue research, build on the foundational mass spectrometry knowledge he accumulated during his Ph.D. and incorporate microbiological techniques to border cells.

“Working on elderberry plants was a good chance for me to start a different project in a distinct plant system, which has been nice,” he said. “And this fellowship will be a great opportunity to apply my current research skills and knowledge base while also developing new abilities.”

For the NIFA fellowship, Kranawetter generated a project narrative, abstract, budget, a logic model, references, and a data management plan, among many other materials. He also utilized a three-member administrative board to support and look over the project in order to assist and give feedback each step of the way.

“This will be a project for me to get out of my comfort zone and gain new expertise compared to what I have done in the lab previously,” Kranawetter said. “It’s nice to have a different perspective when, instead of having a bunch of giant elderberry bushes in the greenhouse, I’m working with three-day-old seedlings.”

The fellowship allots Kranawetter the resources and time he needs to monitor border cell metabolite secretions and their methods of secretion. Kranawetter also observes the bioactivities within an organism living in symbiosis with its pathogens, the microorganisms that cause disease.

“The field of mass spectrometry allows me to apply novel technologies and software systems, while plant sciences allow me to explore the vast diversity of compounds that plants naturally produce,” Kranawetter said.

Kranawetter applies what he knows about border cells in experiments on Medicago truncatula — a close relative to alfalfa — and observes how border cells use their secretions to affect the rhizosphere.

“The question we’re aiming to answer is how are these secretions going into the environment and what role are they playing,” Kranawetter said. “I wanted to get back to my roots with this because as a mostly technical lab, I haven’t done a lot of molecular biology in some instances.”

Kranawetter first removes the seed coat from M. truncatula and sterilizes them in order to protect them from bacterial or fungi contaminants. Next, he places the seeds on a petri dish containing water agar overlaid with sterile filter paper so that the roots remain on top, as opposed to normal methods of plating directly on top of the agar. This ensures that the roots do not penetrate the agar, where border cells would be lost. Although some cells are still lost due to the minimal contact with the filter paper, most remain for later harvest. The final step is to dip the roots in water and harvest border cells — ones that freely come away from their root system — for closer investigation.

As part of his fellowship, Kranawetter is probing for transcripts and proteins associated with metabolite secretion. His results will help determine how border cells affect their environment through their secretions. Kranawetter’s interest in this field stems from his love of plants and technology, both of which he uses in his daily lab work.

“One of the major benefits of being in the Sumner lab is that we’re getting to use very sophisticated instrumentation and applying it to something that we probably would not have been able to examine otherwise,” Kranawetter said.

Kranawetter’s fellowship lasts 2 years, so he hopes this exploration expands our understanding of border cell interactions with the rhizosphere.

“I love this type of research because I get to do a lot of different things! I grow plants, work at the bench, and also use cutting edge instrumentation,” Kranawetter said. “Being able to work in such a diverse manner makes me feel empowered as a scientist.”

Find details on Kranawetter’s fellowship at the USDA NIFA website.

The U.S. Department of Agriculture’s National Institute of Food and Agriculture (NIFA) announced an investment of $12 Million to Advance Research in Agricultural Microbiomes. Microbiome research is critical for improving agricultural productivity, sustainability of agricultural ecosystems, safety of the food supply, carbon sequestration in agricultural systems, and meeting the challenge of feeding a rapidly growing world population. Research supported by the Agricultural Microbiomes in Plant Systems and Natural Resources program area priority within the Agriculture and Food Research Initiative (AFRI) will help fill major knowledge gaps in characterizing agricultural microbiomes and microbiome functions across agricultural production systems, and natural resources through crosscutting projects. AFRI is the nation’s flagship competitive grants program for food and agricultural sciences.

By Sarah Kiefer | Bond LSC

It takes a keen detective to sleuth out why and how particular genetic mutations present the severe symptoms seen in neurological diseases.

The labs of Chris and Monique Lorson are one step closer to understanding one piece in the puzzle for spinal muscular atrophy with respiratory distress (SMARD1) and Charcot Marie Tooth 2S (CMT). They recently identified that the protein ABT1 appears to regulate the activity of IGHMBP2 by means of its interaction with it.

Their NIH-supported studies were recently published in JCI Insight with lab member Gangadhar Vadla as first author.

IGHMBP2 is a protein that causes SMARD and CMT2S. In these two rare neurodegenerative diseases, people inherit a mutated IGHMBP2 gene from each parent. The primary clinical presentation for SMARD1 is respiratory distress and without intervention patients typically die within the first two years of life. CMT2S, while less severe than SMARD1, presents with motor function and coordination defects that substantially impact patients’ lives. SMARD1 and CMT2S patients both demonstrate degeneration of the motor neurons within the brain and spinal cord.

The Lorson’s have built a career out of investigative work, looking into spinal muscular atrophy (SMA), spinal muscular atrophy with respiratory distress (SMARD1), and Charcot Marie Tooth types 1A, 2S and 2E.

When it comes to SMARD1 and CMT2S, understanding how cellular processes are altered when IGHMBP2 is mutated, and how particular mutations present in a clinical setting, is key towards developing therapeutic options.

The Lorson labs approach these studies using genetics and biochemistry. They  generated a series of mice with Ighmbp2 mutations that correlate with patient mutations, showing traits of SMARD1 or CMT2S, depending on what particular Ighmbp2 mutation is present.

“ABT1 is the first protein found to modify the SMARD1 phenotype in mice through its association with IGHMBP2”,  said Vadla, a postdoctoral fellow in the Lorson Lab.

They identified ABT1 as a modifier using an ABT1 gene therapy approach.

“Animals receiving the ABT1 gene therapy showed modest improvements in lifespan and motor function tests, consistent with a modifier, while untreated animals did not, “ Monique Lorson said.

The Lorson lab addressed three primary questions: do IGHMBP2 and ABT1 associate and how stable is this interaction, second, does this interaction change any of the activities associated with IGHMBP2 and, if so, what activities, and, third, can we use this interaction to understand what the role of the IGHMBP2-ABT1 complex is within cells.

“These questions, while seemingly simple, are really important in that is unknown how mutations in IGHMBP2 lead to SMARD1 or CMT2S, “ said Monique Lorson.

Their results demonstrate a strong association between IGHMBP2 with ABT1, and that  binding of IGHMBP2 with ABT1 significantly increases biochemical activity of the IGHMBP2 protein. The studies also provided evidence towards the potential role of this complex in 47S pre-rRNA processing. 47S pre-rRNA processing is necessary to generate ribosomes used in the process of translation. Translation is the process cells use to make proteins.

“Because translation is required to make proteins, if you don’t have proper 47S pre-rRNA processing, some aspects of translation will be significantly impacted, putting the cell under a lot of stress,” said Monique Lorson. “The big goal now is demonstrating that 47S pre-rRNA processing and translational defects are present in Ighmbp2 mutant mice and that these defects result in disease.”

Now, the Lorson lab is testing their findings by creating IGHMBP2 that mirror those seen in real patients to study whether the interaction between IGHMBP2 and ABT1 is altered in any of these mutants.

Why is this finding important?

ABT1 is the first protein found that modifies the severity of disease in Ighmbp2 mutant mice. This is one step towards understanding how IGHMBP2 protein functions within cells and how mutations in IGHMBP2 lead to disease. The progress is only possible with involvement from many Lorson lab members and Bond LSC collaborator Kamal Singh.

“Everyone came together and played an important role, “ Monique Lorson said.  “The Lorson lab works well as a team because we all try to make each other better scientists.”

This project was special to the Lorson family as it was the first time Chris, Monique and their son, Zachary Lorson, published their findings together.

She finds this work maintains her passion for science because she hopes their contributions can someday make a positive impact on SMARD1 and CMT2S families.

“When you feel like you can make a difference and not only impact people’s quantity of health, but also quality of health,” Monique Lorson said. “That makes coming into work really easy.”

Gangadhar P. Vadla, Sara M. Ricardez Hernandez, Jiude Mao, Mona O. Garro- Kacher, Zachary C. Lorson, Ronin P. Rice, Sarah A. Hansen, Christian L. Lorson, Kamal Singh and Monique A. Lorson authored “ABT1 modifies SMARD1 pathology via interactions with IGHMBP2 and stimulation of ATPase and helicase activity.” It appeared in the journal JCI Insight in December 2022.