SPRINT-TB Director Prof. Nicholas Paton and SPRINT-TB Manager Dr. Kristina Rutkute were interviewed by Clearstate, the Economist Intelligence Unit, to share their opinion for a white paper on the Singapore biosciences landscape 2025. The white paper was commissioned by BioSingapore, an industry association for life sciences businesses in Singapore.
The white paper has elicited views from a broad group of industry and research participants, influencers and key opinion leaders about the future of the biosciences industry in Singapore. It assesses trends impacting the biosciences sector, Singapore’s position vis-à-vis regional clusters, and analyses how Singapore should grow industry capabilities in the future. The publication provides themes that can help to guide the development of innovative ideas to propel the next lap of Biosciences growth in Singapore.
The white paper is available for download here.
SPRINT-TB Inaugural Annual Symposium: Advances in Tuberculosis Therapy Research was held at the National University of Singapore on September 18th, 2015.
This was the first in the series of symposiums that SPRINT-TB will host annually, each year featuring renowned local and international scientists, clinicians and key opinion leaders in TB. This year's programme included talks on mycobacterial targets, new TB drug candidates, clinical trials of novel TB treatment regimens, and public health. The symposium welcomed over 100 attendees.
Follow the symposium website www.tuberculosis.sg for announcements of the 2016 event.
View the event photo gallery:
SPRINT-TB staff, students, PIs and collaborators gathered on September 17, 2015 for the programme's first annual retreat. SPRINT-TB holds quarterly meetings for such interactions, while annual retreats present more extensive opportunities for scientific discussion and networking. This years retreat was held at NUSS Kent Ridge Guild House at National University of Singapore.
SPRINT-TB researchers gathered together on September 2, 2015 for the inaugural meeting of the SPRINT-TB Journal Club. This new initiative brings together students, postdocs and research staff across all SPRINT-TB research themes. It will provide an opportunity to present and discuss publications and latest discoveries in the broad TB field, ranging from basic science, microbiology, and medicinal chemistry to clinical research and public health.
The Journal Club, chaired by Dr. Wilfried Moreira (postdoc representative) and Ms. Annanya Shetty (student representative), will meet bi-weekly. The Journal Club details and schedule are available here.
Evidence+ (quarterly publication of National University Health System (NUHS), Singapore) July 2015 issue featured National University of Singapore's BSL-3 facility. SPRINT-TB was reported as a major user of the facility, conducting a range of fundamental and clinical science projects in TB research. Click on the picture above to access the full issue of Evidence+.
National University of Singapore (NUS) BSL-3 Facility was officially opened on Thursday, May 14, 2015 by Singapore's Health Minister Gan Kim Yong. Director of NUS BSL-3 Core Facilities A/Prof Thomas Dick, who also leads SPRINT-TB's Theme 1, was interviewed by Channel NewsAsia after the opening ceremony.
Read the full story here.
Generally mycobacteria are viewed as non-differentiating aerobic bacilli: they do not form specialized resting cells, need oxygen and are rod shaped. Mycobacteria can survive shock starvation in phosphate buffered saline (‘Loebel model’) in a nonreplicating state without any apparent morphological differentiation.
SPRINT-TB Theme 1 researchers had another look at this adaptation. Rather than shock starving the bacilli in saline, they added traces of a carbon source to the saline and observed the response of the bacteria. Interestingly, providing traces of a carbon source to M. smegmatis in saline (as opposed to shock-starving the microorganism), resulted in the formation of a small-cell morphotype: reductive cell division generated very short rodshaped cells with increased long-term viability. Upon addition of rich medium, these small resting cells grew back to larger standard cells before commencement of the regular cell division cycle. The fact that a new morphotype can be so easily generated by slight changes in culture conditions supports the notion of a surprising morphological plasticity of mycobacteria.
These observations were described in Future Microbiology in April 2015 (Wu ML, Dick T. Metabolic flexibility and morphological plasticity in mycobacteria. Future Microbiol. 2015 Apr;10:449-52).
Perchlozone®, a new thiosemicarbazone class drug, was approved for treatment of multidrug-resistant tuberculosis (MDR-TB) in Russia in 2012. The mechanism of action of the drug was at the time unknown.
Another thiosemicarbazone is a well-studied old TB drug thiacetazone. It is known to inhibit the FASII dehydratase complex HadABC, which is involved in cell wall biosynthesis in Mycobacterium tuberculosis. Thiosemicarbazone is a prodrug requiring activation by the monooxygenase EthA.
SPRINT-TB Theme 1 performed a comparative in vitro analysis of both drugs. The two compounds were found to have an identical spectrum of activity. Spontaneous drug-resistant mutants exibited cross-resistance, which was mapped to HadABC and EthA, thereby suggesting that perchlozone, like thiacetazone, is activated by EthA with its principal target being HadABC.
The study was published in the International Journal of Antimicrobial Agents in April 2015 (Gopal P, Dick T. The new tuberculosis drug Perchlozone shows cross-resistance with Thiacetazone. Int J Antimicrob Agents. 2015 Apr;45(4):430-3.)
SPRINT-TB Theme 1 researchers identified bortezomib (or Velcade®, which is currently approved for treatment of multiple myeloma), as a novel whole-cell active mycobacterial caseinolytic protease (Clp) inhibitor. Clp constitutes a key degradative proteolytic machinery involved in central proteome homeostasis in Mycobacteria. Clp was found to be potently inhibited by bortezomib and its derivatives, followed by mycobacterial growth inhibition. The discovery established Clp as a new validated drug target and bortezomib as an attractive lead compound for the development of new tuberculosis drugs. Bortezomib and its derivatives are currently under further pre-clinical investigation.
A provisional patent application for the repurposed use of bortezomib was filed on February 6, 2015. This invention is a product of collaboration between Eric Rubin’s group at Harvard School of Public Health (USA), the Experimental Therapeutic Center - A*STAR (Singapore) and Thomas Dick’s group at Department of Microbiology, National University of Singapore (Singapore).