Dr. Gangadhara Vadla, a postdoctoral associate in the Lorson lab uses the NIH S10-funded circular dichroism machine to determine the secondary structure of the protein of his interest.
Structural biology is the study of how biological molecules are built. By studying how the molecules in the human body are assembled, how they function and how they interact, scientists can learn more about how to keep us healthy.
Studying these molecules requires highly specialized instruments and facilities. The University of Missouri’s Molecular Interactions advanced technology core facility (MIC) provides state-of-the-art equipment and expertise for characterizing molecular structure, understanding what binds molecules together and creating new molecules and proteins.
Synthesizing new proteins (novel peptides and peptidomimetics) could enhance medical imaging techniques, lead to new biomaterials for nanomedicines and aid antiviral drug development.
Since 2017, the MIC has assisted researchers across the UM System and external clients with their needs to develop new therapeutic and imaging agents as well as characterizing the underlying basic science of their research projects.
What services does the MIC provide?
The Molecular Interactions Core provides services for academic and commercial clients to determine interaction patterns between the targets (usually proteins) and ligands (small molecules, DNA, RNA, peptides, etc.). The binding affinity (and specificity) of drug-like compounds with a given target helps to develop drugs against a variety of pathogens and cancers. Additionally, the MIC provides services to determine the secondary and tertiary structures of ligands (usually peptides) and targets (proteins and/or nucleic acids) important in biomedical research. The MIC facilitates nanoparticle research by helping users to determine zeta-potential of nanoparticles. The MIC also provides services for peptides and peptide-like compounds (peptidomimetics) for novel biomaterials, nanoparticles and cancer imaging and therapeutic agents.
Kaylee Klaustermeier, a technical associate in Singh lab uses a microscale thermophoresis machine (Monolith NT.115) to determine the binding affinity of anti-cancer drugs with human DNA polymerase θ.
The specific services offered are:
Circular dichroism
Custom LC-MS
Crystallography
Dynamic light scattering
Peptide synthesis
Protein-protein and protein-ligand interaction
Protein purification
Nanodisc preparation
Drug-design and discovery
Which areas can benefit the most from your services?
Chemistry, biochemistry, immunology, virology, plant science, bioengineering, translational medicine, biomaterials, physics, veterinary medicine, radiochemistry, environmental science and drug-design.
How has the MIC evolved since 2017?
The MIC has added several new instruments, including a circular dichroism machine funded by a National Institutes of Health S10 grant. The MIC has helped MizzouForward faculty by acquiring new instrumentation including a Jasco CD machine, Jasco FTIR machine, Jasco UV-Vis machine, Jasco fluorometer capable of anisotropy and fluorescence resonance energy transfer measurements, enabling their use by researchers across campus.
The peptide/peptidomimetic operations of the core were founded to meet the demand for synthesis of novel peptide-like compounds that could not be easily synthesized or obtained commercially. Acquisition of a multiple peptide synthesizer and other equipment has enabled the peptide/peptidomimetic operation to grow in both the diversity of compounds offered and the scale of production to support needs from basic research to clinical trials.
Who on campus is using the core for their research?
Several researchers at MU are using the core to aid their work. Three examples:
Carolyn Anderson, professor of radiology: The peptide core prepares a variety of peptidomimetics for Anderson’s group at the Molecular Imaging and Theranostics Center, which are used in cancer research and treatments.
Bret Ulery, associate professor of chemical engineering: The MIC provides several labeled long molecules used by his research group to focus on the design, development and production of novel biomaterials for a variety of biomedical applications primarily in the fields of immunology and regenerative medicine.
Michael Petris, Professor of Biochemistry and Ophthalmology: The MIC provides drug-like compounds that are important in cancer therapeutics. The MIC helps in determining the binding affinity of these compounds with the target molecules. This project has been funded by NIH through an R01 mechanism.
What types of external researchers use the MIC?
Because the MIC’s capabilities are quite unique, the core also provides services for external researchers and commercial entities. For example, The MIC has been providing services for international researchers at the Karolinska Institute in Stockholm, Sweden, as well as for those working for companies such as Sanctum Therapeutics Corp. in Sunnyvale, California.
The peptide/peptidomimetic operation is internationally known for its synthetic capabilities and prepares compounds for researchers both at MU and around the world. Peptidomimetics are routinely shipped to Memorial Sloan Kettering Cancer Center, Cornell University, University of Colorado, University of the Republic-Uruguay and Endevica Bio for biomedical applications including cancer imaging and therapy research.
How should researchers request services?
Researchers can contact the staff for computer-aided drug design, molecular interaction instrumentation and peptidomimetics consultations. The MIC has individuals with extensive expertise in these areas. Currently researchers request services by emailing Director Kamal Singh at (ksingh@missouri.edu) or Fabio Gallazzi, research associate professor in the Department of Chemistry at (gallazzif@missouri.edu) for peptidomimetic syntheses.
You also can email mulscmicore@missouri.edu to book a time slot to use the various machines, for hands-on learning and general inquiries.