Community Collaborations

Matthias Truttmann, PhD Assistant Professor, Molecular & Integrative Physiology and Nicholas Urban, PhD Candidate, Molecular & Integrative Physiology

Standing in an open clearing, we watched as Bob Douglas, a retired Science teacher turned llama farmer, introduced us to our animal collaborator. “This is him. This is Moment,” Bob said as Moment of Victory stood grazing on the grass. We stood admiring the elegant sevenfoot-tall animal with a large neck and bulging eyes enjoy his surprise mid-day snack. The llama had a similar build to a miniature, furry giraffe. They are much larger in person than one may think.

Why were we, a UM assistant professor (Dr. Matthias Truttmann) and his graduate student (Nicholas Urban), standing in the middle of a llama farm on a hot summer day in Dexter, Michigan? We were leading an interdisciplinary and interdepartmental team to develop novel tools to help study a variety of important scientific questions. We were in the pursuit of developing nanobodies to help us study in unprecedented detail proteins involved in these diseases. But why did we need llamas?

In addition to their uniquely sassy attitudes, llamas have a special immune system. In mammals, the immune system protects us from infections of bacteria, viruses, and fungi. Important components of the immune system are “antibodies”, which bind specifically to these microscopic invaders to help kill and remove them to keep us healthy. In biomedical research, these antibodies can be generated against specific targets, allowing us to visualize and study these proteins in a variety of laboratory applications. Llamas, alpacas, and other camelids are unique as they have an immune system that produces a special type of antibody (a “Small” antibody), which is not found in humans. Through manipulation in the laboratory, we are able to collect and harness only the genes of the protein-binding regions of these small antibodies. We call these fragments nanobodies (Figure 1).

Nanobodies offer many unique benefits for use in research. They are 1) much smaller in size compared to traditional antibodies, and thus can bind to more difficult to reach proteins, 2) stable and easy to store, 3) significantly cheaper to produce compared to regular antibodies, and 4) versatile and can be used in various biomedical research and treatment applications. For example, nanobodies are used to make SARS-CoV2 virus particles visible on human cells or to follow by positron emission tomography (PET) scanning how immune cells infiltrate metastatic tumors in a living animals, a technique about to be adapted for clinical use in human cancer diagnostics.

genes out of nanobody-producing cells (Figure 2). Importantly, the entire process was pain-free and without complications for Moment of Victory, who remained with his herd throughout the immunization process. In Dr. Truttmann’s lab, we generated a nanobody library, which we then screened for nanobodies that only bound our proteins of interest.

genes out of nanobody-producing cells (Figure 2). Importantly, the entire process was pain-free and without complications for Moment of Victory, who remained with his herd throughout the immunization process. In Dr. Truttmann’s lab, we generated a nanobody library, which we then screened for nanobodies that only bound our proteins of interest.

In addition to generating innovative tools for our own research, this project also highlights the excellent collaborative community of the University of Michigan: Dr. Brooke Pallas (ULAM) performed the immunizations and collection of llama blood samples; the protein cocktail used for immunizations contained proteins of interest to several UM research groups, including the Shah, Tessier, Wang, Lieberman, Osawa, and Truttmann labs. Thus, nanobodies from this single llama immunization campaign will support ongoing cancer and neurodegeneration research in our department and elsewhere at UM; and finally, the role of our community collaborator and owner of Moment of Victory, Bob Douglas, cannot be overstated. Without his commitment, generosity, and curiosity to support our research, this project would not have been possible. We all enjoyed learning more about llama biology during our numerous visits to Bob’s farm last summer, one of the rare highlights in an otherwise challenging year. Altogether, this project could not have been completed without the efforts of these numerous individuals and groups.

The labs involved in this project would like to thank Bob Douglas and Moment of Victory for their contributions to UM science and research! If you would like to learn more about our nanobody-based research and/or support it, please visit: https://truttmann. lab.medicine.umich.edu/.