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Modeling Stem Cell Behavior for Advancing Novel Tendon Therapies

Project Directors: Kyle Harrington, Nathan Schiele

Project Team: Leo Epstein, Sophia Theodossiou, Aniruddha Belsare

Tendons are collagen-rich musculoskeletal tissues that transfer mechanical forces from muscle to bone to allow for normal human movements, such as locomotion. Unfortunately, tendon injuries are frequent, treatment options are limited, and the mechanical function of tendon rarely returns to pre-injury levels.

Recent efforts to develop engineered tendon replacements and improve tendon healing have focused on using mesenchymal stem cells (MSCs). However, these engineered tendon tissues have yet to match the structure and mechanical function of native tendons. Thus, there is a critical need to identify the mechanisms that direct tenogenesis (differentiation toward tendon) and tendon formation by MSCs before effective regeneration tendon approaches can be developed.

The team’s long-term goal and innovative approach is to advance tendon healing by identifying developmentally guided mechanisms that regulate tenogenesis in MSCs for use in engineered tissues and regenerative medicine.

In order to determine what role the cell network plays in regulating MSCs to form tendon, 2 computational models will be explored:

  • an image-based model at the single cell scale, and
  • a cell-cell network model.
Modeling Access Grants

Robot Facilitates Research

CMCI funds were used recently to purchase this ROTOR HDA, high-throughput microbial array pinning robot, to facilitate microbial evolution research on campus.

Quoted by the manufacturer as the fastest and most powerful colony manipulation robot in the world, this machine is indeed ultra-fast and easy to use. The ROTOR HDA is designed for the picking and re-plating of microbial cells and viruses in various size arrays and can operate with cells grown on solid agar or in liquid media. It uses a robotic arm and plastic replica plating pads to pick up samples of cells from culture plates. The robotic arm then moves to a new “target” plate and deposits the cells. Operating the machine simply requires the user to select an appropriate program from a drop-down menu.

So far, the beneficiaries of this purchase are The Rowley Laboratory and the Wichman Lab.

Research Projects

Modeling Access Grants Announcement

Aniruddha Belsare, Ph. D. has recently joined the cohort of postdoctoral fellows in the CMCI Collaboratorium and is available to help with appropriate Modeling Access Grants (see below). Aniruddha is a disease modeler with a background in veterinary medicine, disease ecology, and conservation research. He uses an agent-based modeling approach to investigate complex host-pathogen systems. He is interested in expanding the applications of agent-based models to other research areas including, but not limited to, biomedical research (molecular biology, cell biology, cancer biology), public health research (healthcare management, social dynamics) and epidemiological research (antimicrobial resistance, zoonotic/vector-borne diseases).

The Modeling Access Grant Program enables faculty to produce preliminary biomedical models for competitive external proposals using support from the Center for Modeling Complex Interactions (CMCI) Collaboratorium. This program is intended for faculty with modeling needs outside of their own area of expertise who would like to develop a modeling component to a research project and who intend to submit a proposal within the next year. The objective is to substantially strengthen the work by adding the modeling dimension. The access grant will provide dedicated time with Collaboratorium personnel for developing models, preparing the modeling aspects of a grant proposal, and potentially write a manuscript.

Applicants are expected to consult with the CMCI Project Coordinator (Celeste Brown, celesteb@uidaho.edu) prior to developing a proposal to obtain advice on whether current Collaboratorium resources match the investigator’s needs. Proposals will be accepted anytime during the year, and the review process is simplified and expedited as described below.

Instructions for Proposal

Modeling Access Grants, Resources

McMaster Project

Project PI: Jagdish Patel

This research project is to identify the correct bound conformations of veranamine in signma-1 and 5HT2B receptors. Crystal coordinates of sigma-1 and 5HT2B receptors will be downloaded from the Protein Data Bank. Both of the receptor structures will then be used to perform ordinary molecular dynamics to sample various conformations available. Docking software will be used to dock veranamine to 100 snapshots obtained from molecular dynamics simulations of each receptor to determine the pocket heavily populated with high scoring poses. Highly populated pose of veranamine in both receptors will be refined using flexible docking to obtain the final best bound conformations. Structural analogs will be docked directly to the predicted binding site of veranamine using a docking software.

Externally Funded Projects