NEW YORK (Jan. 10, 2013) -- Despite major advances in high-throughput screening and genomic technologies, tuberculosis (TB) drug development remains hindered by a general inability to measure the effective penetration of chemical compounds into Mycobacterium tuberculosis bacteria (Mtb) which cause TB. To address this gap, the Tres Cantos Open Lab Foundation has awarded Weill Cornell Medical College funding to support a visiting Weill Cornell microbiologist's two-year research project at the Tres Cantos Open Lab in Spain to measure and analyze the permeability of chemical compounds into Mtb using novel metabolomics technology.
The new Open Lab research project seeks to identify broader chemical principles that could be used to transform potential potent chemical inhibitors into active drugs, a key bottleneck in current anti-infective drug research. The goal of the research project will be to monitor the intracellular accumulation of diverse potential drugs and reveal the associations between cell permeability and anti-TB activity using metabolomics technology developed by Weill Cornell.
The Tres Cantos Open Lab is based at GlaxoSmithKline's (GSK) Tres Cantos Medicines Development Campus in Spain. Dr. Saki Raheem, a post-doctoral researcher at Weill Cornell, will work as an Open Lab Scientist in an integrated team alongside researchers from GSK and will have access to resources, chemical compounds and laboratory space to perform this novel TB research project. During his time at the Open Lab, Dr. Raheem will screen and analyze hundreds of potential anti-tuberculosis compounds from GSK's compound library. As a result, this research may lead to the advancement of TB drug development by informing researchers on the predictive physicochemical characteristics needed for a given compound to effectively permeate Mtb.
"This is a project that will help to understand what chemical properties are needed for activity against Mtb," says Professor Sir Leszek Borysiewicz, trustee and chair of the Governing Board at Tres Cantos Open Lab Foundation. "It could set the foundations to design better anti-TB drugs."
This new research at the Open Lab builds upon findings published in Science in November by infectious disease expert Dr. Kyu Rhee, who is Weill Cornell's principal investigator for this Open Lab research project. The recent study demonstrated current mass spectrometry technologies could be repurposed to study existing TB drugs and directly visualize what happens as they infiltrate TB cells. This study was the first to show mass spectrometry technology can be adapted to understand the action of antibiotics on living, intact bacterial cells. Researchers "watched" at a basic biochemical level how one TB drug was able to both enter and inhibit Mtb, while another drug's failure to inhibit Mtb was found to be due to its extensive degradation once inside, rather than its inability to enter the bacterium.
"We have adapted our metabolomic tools to monitor the intracellular accumulation, transformation and biochemical events of currently available drugs against Mtb. As a result, mass spectrometry can now be used to test new chemical compounds, as well as the current cocktail of drugs used to treat TB, and find ways to improve them," says Dr. Rhee, who is also an associate professor of medicine in the Division of Infectious Diseases and associate professor of microbiology and immunology at Weill Cornell. "With mass spectrometry, and now the latest metabolomics assay we developed and are testing, we aim to design and test the much-needed next generation of effective anti-TB agents."
This new research project is the second project by Weill Cornell in the Tres Cantos Open Lab. In 2011, Dr. Carl Nathan, chairman of the Department of Microbiology and Immunology, the R.A. Rees Pritchett Professor of Microbiology and the director of The Abby and Howard Milstein Program in the Chemical Biology of Infectious Disease at Weill Cornell, sent Dr. Thulasi Warrier, a postdoctoral fellow in the Nathan Lab to work for a year at the Open Lab. There, using an assay developed at Weill Cornell, Dr. Warrier successfully screened 269,000 GSK compounds against TB. This November, a second postdoctoral fellow from the Nathan Lab, Dr. Landys Lopez-Quezada, arrived in Tres Cantos to continue the Open Lab research project begun by Dr. Warrier.
Tres Cantos Open Lab Foundation
The Tres Cantos Open Lab Foundation is focused on providing funding and support for scientists, academics and institutions to develop and advance new ideas that could lead to new medicines to treat diseases of the developing world. Researchers are invited to submit projects for collaboration and funding, to be reviewed by the Foundation's Governing Board and Trustees. http://www.
Weill Cornell Medical College
Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu.