Principal Supervisor: Professor Ruth Luthi-Carter, Dept. of Neuroscience, Psychology & Behaviour
Second supervisor: Professor Sergey Piletsky, Dept. Of Chemistry
Non-academic partner: MIP Diagnostics Ltd. (MIPD)
Project Title: Molecularly Imprinted Polymers (MIPs) for specialised brain cell targeting and imaging
Background and Rationale: Genetic and biochemical analyses of the aetiopathologies of central nervous system (CNS) diseases have demonstrated the need to be able to target cellular proteins other than enzymes and receptors. Targeting these molecules in peripheral tissues has largely been solved by antibody-mediated strategies but a parallel approach to accessing the CNS has not (yet) proven satisfactory. One new and promising strategy involves the chemical functionalization of MIPs, which can target a wide range of molecular structures. MIPs also have the strategic advantages over conventional antibodies that they are chemically stable and amenable to functionalization.
The overall goal of this project is to develop novel approaches and proprietary technology relating to nanoMIP delivery that will be relevant for a wide variety of CNS applications. Here we address specific key hurdles to MIP delivery to the CNS – the functionalization of MIPs to facilitate their crossing the blood-brain-barrier (BBB) and targeting diagnostic or therapeutic entities to specialised brain subcompartments and molecular functions.
The Specific Aims of the project are:
Aim 1: To develop MIP nanoparticles (nanoMIPs) with chemical functionalities that allow them to traverse the blood-brain-barrier (BBB). Based on known principles of BBB permeability, a set of quantum dot-labeled nanoMIPs will be synthesised and tested for BBB permeability following IP injection in rats and mice.
Aim 2: To develop nanoMIPs that target brain-cell-type-specific surface proteins, based on previous gene expression data from the Luthi-Carter lab. nanoMIPs will be synthesized to target cell- and cell-compartment (e.g. synaptic) proteins and tested for their ability to target corresponding cell populations in vitro and in vivo.
Aim 3: To develop appropriately labelled MIPs to allow enhanced visualisation of brain structure/function in vivo. MIPs will be developed to detect molecular entities and processes that monitor brain function and the aetiologies of CNS injuries and diseases. This will involve producing MIPs that bind to aggregation-prone proteins, and detect inflammation-, signalling- and metabolism-related cell changes in neural cells.
Closing date for applications: 7th January 2018
Interview dates: February 2018 TBC