Group: Targeted therapeutics and nanodevices and Respiratory, cardiovascular and renal pathobiology and bioengineering”
Group leader: Silvia Muro (firstname.lastname@example.org) and Ramón Ferrer(email@example.com)
Type B Niemann-Pick disease (NPD-B) is a rare, inherited and debilitating disease caused by mutations affecting the enzyme sphingomyelinase, where cells accumulate lipids such as sphingomyelin and cholesterol in their lysosomes and membranes, resulting in multiple biochemical and cellular disfunctions throughout the body. Importantly, the lungs are a primary target for NPD-B intervention, since respiratory alterations are reported to be a major cause of death in patients. However, the links between the genetic and biochemical changes in the NPD-B lung and the biomechanical alterations that lead to respiratory disfunction are unknown. The Farré Lab has developed state-of-the-art models and tools to investigate the mechanical properties of the lungs at the organ and cellular levels, destined to improve diagnosis and treatment of respiratory diseases. In addition, enzyme replacement therapy by i.v. infusion of recombinant sphingomyelinase is under clinical trial, but early results have shown suboptimal accumulation of this pharmaceutical in the lungs and high doses used to overcome this rendered considerable side effects. The Muro lab has developed polymer nanoparticles targeted to a cell-surface molecule highly expressed on the diseased lung (ICAM-1) which efficiently deliver (by 1-2 orders of magnitude) acid sphingomyelinase to this organ. This project will unite both the Muro and the Farré labs’ efforts to achieve both fundamental and translational goals: 1-to investigate the biomechanical abnormalities associated to NPD-B and offer a link for the genetic and biochemical deficiencies observed, helping prognosis predictions, and 2-to evaluate the efficacy of novel nanoparticle-mediated enzyme replacement therapy on restoring normal biochemical and mechanical functions in the lungs.
Job position description:
The candidate should have an interdisciplinary profile, including previous training (BS and MS) in fields relative to the topics described above, such as biomedicine, biophysics, nanoscience, pharmacy, etc. He/she will be involved in investigating the biomechanical properties of the NPD-B lung using ex vivo lung models and cell cultures approaches, atomic force microscopy, magnetic tweezers, cell stretching, nano-patterning, traction microscopy, etc. Also, the candidate will be involved in the fabrication and testing of polymer nanoparticles loaded with therapeutic enzymes, including dynamic light scattering, gel permeation chromatography, biochemical measurements, fluorescence microscopy of cell cultures, and in vivo (mouse) injections and tissue harvesting, etc. It is also expected that the candidate will participate of and benefit from regular laboratory tasks, including housekeeping, safety compliance, record keeping, writing of publications, attendance to lab meetings and conferences, and general assistance and participation in the activities of the involved labs. Good skills on communication, teamwork, proactivity, commitment, integrity, time management, critical and analytical thinking will be highly evaluated. The selected candidate will receive all necessary training for the mentioned techniques and will develop the experimental work in the facilities of IBEC and UB, at the labs of Prof. Muro (aim 2) and Prof. Farré (aim 1), respectively.