Columbia Technology Ventures

Inhibition of circadian regulation or mTOR complex increases immunity against bacterial infection

This technology describes a previously unstudied connection between circadian rhythm, immunity, metabolism, and the mTOR complex 2 (mTORC2), which can be used to fight bacterial infections.

Unmet Need: Molecular target linking tolerance with circadian rhythm to fight infection

Systemic bacterial infections present a significant problem, especially with the rise of antibiotic-resistant bacteria. Currently, there is a shortage of new antibacterial treatments that can circumvent resistance to commonly-used antibiotics. There are two distinct, complementary strategies by which host organisms combat bacterial infection: resistance mechanisms, which control bacterial growth; and tolerance mechanisms, which allow the host to survive the pathological effects of infection. Inhibition of the host TORC2 complex has been demonstrated to increase host survival of bacterial infection. As such, this technology can be developed as a host-targeted therapeutic with the potential to increase survival of infection even by multidrug-resistant bacteria.

The Technology: Specific pharmacological target to fight multidrug-resistant bacterial infections

This technology describes a previously unstudied connection between circadian rhythm, immunity, metabolism, and the mTOR complex 2 (mTORC2), which can be targeted to fight bacterial infections. Inhibition of mTORC2 leads to improved survival of diverse bacterial infections via metabolic mechanisms. Furthermore, disruption or manipulation of the circadian rhythm can also significantly increase immunity against infection. Thus, this technology provides a method of improving bacterial resistance, particularly useful for combating infections that are resistant to traditional antibiotics. Additionally, mTORC2 has known functions in glucose homeostasis and apoptosis, providing additional applications of this technology as a therapeutic target for metabolic disorders and cancer. Finally, this technology can also be utilized as a research tool to further investigate the relationship between circadian rhythm, immunity, and potentially other disorders.

This technology has been tested in vivo in Drosophila mutants.

Applications:

  • Small molecule drug to fight infections involving multidrug-resistant bacteria
  • Therapeutic target for metabolic disorders
  • Therapeutic target for cancer
  • Research tool to study link between circadian rhythm and immunity
  • Research tool to study a specific protein which regulates circadian rhythm

Advantages:

  • Provides innovative molecular target for combating multidrug-resistant bacteria
  • Expands methods for addressing bacterial resistance

Lead Inventor:

Michele Shirasu-Hiza, Ph.D.

Patent Information:

Patent Status

Related Publications:

Tech Ventures Reference:

  • IR CU16116

  • Licensing Contact: Ron Katz