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NANOPARTICLES FOR DELIVERY OF TISSUE INHIBITOR OF MATRIX METALLOPROTEINASES TO THE BRAIN AS MEANS TO AMELIORATE CONSEQUENCES OF ISCHEMIC CELL DEATH
Supervisor:
Prof. Leszek Kaczmarek, Ph.D
Supervisor webpage
http://neurogene.nencki.gov.pl/
Foreign partner:
B. Sreedhar, Ph.D, Indian Institute of Chemical Technology (IICT), Hyderabad, India
Foreign partner webpage:
http://www.iictindia.org/
Background:
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases acting outside the cells and therefore attributed with digesting extracellular matrix components. In particular, MMP-9 (gelatinase B, 92kDa type IV collagenase) is produced in a latent form in the cell and after release to extracellular space; it is activated by cleavage off the propeptide. Tissue inhibitor of matrix metalloproteinases 1, also known as TIMP-1, is known to bind MMP-9 with high affinity and to block its enzymatic function. Enhanced expression and activities of MMPs have been observed under numerous pathologic conditions including stroke. Thus, inhibition of MMPs is considered as a potential therapeutic target. Today there is only one FDA-approved treatment for ischemic stroke; i.e., the serine protease tissue-type plasminogen activator (tPA). Combination therapies of tPA with MMP-9 inhibitor may be useful for decreasing the risk and severity of complication in thrombolytic therapy. Previous studies suggest that TIMP-1 can play a neuroprotective role in cerebral ischemia by inhibiting MMP-9. But TIMP-1 being large protein cannot cross the BBB therefore we plan to use a nano-biotechnological approach for targeted deliver of TIMP-1 into brain using nanoparticles.
Aim of the study:
The aims of the project are: 1) To develop a nanoparticles for targeted delivery into brain; 2) To deliver TIMP-1 through these nanoparticles; 3) Explore whether targeted delivery of TIMP-1 into the brain can be a functional strategy to inhibit MMP-9.
International exchange:
During his/her stay in India, the PhD student will be working for development of nanoparticles as per schedule: 1) First year –Design of nanoparticles which can cross BBB (loaded with GFP); 2) Second year - Design of nanoparticles which can cross BBB (loaded with TIMP-1); 3) Third Year – If needed testing further modification in nanoparticles. During the stay the student will have opportunities to learn following techniques: KRATOS AXIS 165 Electron Spectroscopy for Chemical Analysis (ESCA), TECNAI FE12 Transmission Electron Microscope (TEM), Atomic Force Microscope (Veeco), Electron Spin Resonance (ESR), Lyophilizer, Zeta Sizer, High pressure homogenizer, UV-Vis-NIR DRS Spectrometer (Perkin Elmer), FTIR Spectrometer (Bio-RAD), ICP-AES (Thermo), Particle Size Analyzer (Malvern Mastersizer 2000), Atomic Absorption Spectrometer (Perkin Elmer AAnalyst 300)
Additional requirements for the student:
Education: master degree in science, especially biology or medicine. The person should be dedicated, bright, and hard-working. Prior expertise in nanoparticles will be an advantage.


Rekrutacja na studia doktoranckie Instytutu Nenckiego

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