Area of knowledge: Biotechnology and Nanotechnology
The ability to navigate the human body and access all its compartments without causing any damage is an essential requisite for therapy and diagnostics. Among the different organs, the brain is one of the most important yet arduous to enter with unique physiology. The brain’s high energy metabolism and sensitivity to external insult require a specialised vasculature, often known as the blood-brain barrier (BBB), inaccessible to most known drugs. It is thus paramount to design new strategies to cross the BBB to either deliver therapeutic load or probe the brain complexity.
One promising approach involves the design of nanoscopic carriers capable of penetrating the BBB via receptor-mediated transcytosis. Within the Molecular Bionics Group (led by Giuseppe Battaglia, GB), we have been studied such a transport mechanism in great detail and disclosed critical structure/function correlations (Tian et al. Science Adv. 2020, 10.1126/sciadv.abc4397). Here we propose to join forces with the Smart nano-bio-devices (led by Samuel Sanchez, SS), a leading group in nanorobotics, to design a unit capable of penetrating the BBB and navigating the brain. The aim will be to adapt biocompatible nanorobots made of mesoporous silica nanoparticles (Hortelao et al. Science Robot. 2021 10.1126/scirobotics.abd2823) to react to brain metabolites. We will equip them with relevant enzymes, including glucose oxidase, glutamate decarboxylase, or aspartoacylase, to detect and follow glucose, glutamate, or N-acetyl aspartate. These metabolites are critical for brain function.
We will combine soft matter physics and material science with neurophysiology and biophysics to engineer a completely new way to probe brain metabolism.
JOB POSITION DESCRIPTION
We seek candidates either with physical and engineering background interested in neuroscience, or with life science background interested in nanotechnology and nanorobotics. The student will be trained in nanofabrication of nanorobots, using well established protocols developed within the SS group, as well as to study their anomalous diffusion using both advanced optical and electron microscopy methods. As the nanorobots are optimized in vitro, they will be tested and their diffusion, we will study them in relevant animal models, including healthy, glioma bearing and Alzheimer models, all available within GB labs.
We aim to exploit unique nanorobots features such a swarming, chemotaxis, and hydrodynamic coupling to map out how these metabolites are distributed within healthy and diseased brains. We will initially administer the nanorobots directly into the brain, using stereotactic injections as well as to functionalise them with the ability to cross the BBB. We will thus be using both in vivo and ex vivo imaging methods to assess the brain distribution.