Originally, this project of two subjects PrimeCell and Cambridge Biological (UK) is based on an observation that symptoms of female Rheumatoid Arthritis patients are alleviated during pregnancy but re-appear 3 to 5 months after delivery. During the study of immune response in pregnant women, two soluble proteins produced by trophoblast cells from placenta were discovered. One is sFlt-1, a well known anti-angiogenesis molecule. When sFlt-1 binds to VEGF, it inhibits the biological function (angiogenesis) of VEGF. The other is sCD26, an enzyme that controls several biological functions through its activity on quite a few cytokines and growth factors. These functions include angiogenesis, inflammation, anorexia and pain. We have done experiments to show that sCD26 can modulate inflammation.
Řešitelé jsou PrimeCell a Chelotech (Izrael). Dojde k použití kultivace lidských buněk, testování toxicity vyvíjené látky TPENGIN na lidských buněčných kulturách s použitím metod molekulární biologie jako je PCR, WB, ELISA. Bude provedena studie proof-of-concept simulující průběh výše uvedených ischemických příhod u lidí. Tyto metody jsou jediné možné pro uskutečnění translace do aplikovaného výzkumu, jenž vede k vývoji nového léčebného přípravku (prototypu v GMP kvalitě) a podkladů pro nový léčebný postup.
This project proposes to develop a new method for targeting ant-tubercular agents to their site of action inside the bacterium. I am well-equipped to contribute to this study, having run a drug discovery group in TB for the past 11 years. In addition, I have >25 years of experience in mycobacterial research, including molecular genetics, gene regulation, cell wall biosynthesis, and antibiotic resistance. I run the TB Discovery Research group at IDRI, managing and directing the research of a multi-disciplinary team directed towards early stage drug discovery, including target identification and validation, target-based and whole-cell screens, medicinal and synthetic chemistry, hit and lead chemistry, compound optimization and candidate selection. Work has included the development and implementation of biochemical and whole cell screens, and high content screening (using virulent M. tuberculosis under BSL3 conditions), as well as evaluation of several hit series arising from these and other screens. In addition, we have a strong program in biology targeted towards an increased understanding of metabolic pathways and cell death mechanisms.