Jaydeep Unni, Ph.D.
Sr. Project Manager, Robert Bosch Healthcare Systems, Palo Alto, CA
Remote Patient Monitoring – Challenges and Opportunities
Remote Patient Monitoring (RPM) is gaining importance and acceptance with rising number of chronic disease conditions and with increase in the aging population. As instances of Heart diseases, Diabetes etc are increasing the demand for these technologies are increasing. RPM devices typically collect patient vital sign data and in some case also patient responses to health related questions. Thus collected data is then transmitted through various modalities (wireless/Bluetooth/cellular) to Hospitals/Doctor’s office for clinical evaluation. With these solutions Doctors are able to access patient’s vital data ‘any time any where’ thus enabling them to intervene on a timely and effective manner. For older adult population chronic disease management, post-acute care management and safety monitoring are areas were RPM finds application. That said, there are significant challenges in adoption of Remote Patient Monitoring including patient willingness and compliance for adoption, affordability, availability of simpler/smarter technology to mention a few. But experts contend that if implemented correctly Remote Patient Monitoring can contain healthcare expenditure by reducing avoidable hospitalization while greatly improving quality of care.
V. Nagaraja Ph.D.
Professor, Indian Institute of Science, Bengaluru, India
Perturbation of DNA topology in mycobacteria
To maintain the topological homeostasis of the genome in the cell, DNA topoisomerases catalyse DNA cleavage, strand passage and rejoining of the ends. Thus, although they are essential house- keeping enzymes, they are the most vulnerable targets; arrest of the reaction after the first trans-esterification step leads to breaks in DNA and cell death. Some of the successful antibacterial or anticancer drugs target the step ie arrest the reaction or stabilize the topo -DNA covalent complex. I will describe our efforts in this direction – to target DNA gyrase and also topoisomerase1 from mycobacteria. The latter, although essential, has no inhibitors described so far. The new inhibitors being characterized are also used to probe topoisomerase control of gene expression.
In the biological warfare between the organisms, a diverse set of molecules encoded by invading genomes target the above mentioned most vulnerable step of topoisomerase reaction, leading to the accumulation of double strand breaks. Bacteria, on their part appear to have developed defense strategies to protect the cells from genomic double strand breaks. I will describe a mechanism involving three distinct gyrase interacting proteins which inhibit the enzyme in vitro. However, in vivo all these topology modulators protect DNA gyrase from poisoning effect by sequestering the enzyme away from DNA.
Next, we have targeted a topology modulator protein, a nucleoid associated protein(NAP) from Mycobacterium tuberculosis to develop small molecule inhibitors by structure based design. Over expression of HU leads to alteration in the nucleoid architecture. The crystal structure of the N-terminal half of HU reveals a cleft that accommodates duplex DNA. Based on the structural feature, we have designed inhibitors which bind to the protein and affect its interaction with DNA, de-compact the nucleoid and inhibit cell growth. Chemical probing with the inhibitors reveal the importance of HU regulon in M.tuberculosis.