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Institute for the Physics of Living Systems

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Research Projects Available 2022

Please feel free to contact supervisors if you would like more information on a project.

Antimicrobial crack propagation in bacterial membranes

Supervisor: Bart Hoogenboom | eligible for BioP, Brian Duff and IPLS studentships | on campus project
Membrane-targeting antimicrobials are being pursued as next-generation antibiotics. In this project, we will focus on previously recorded atomic force microscopy (AFM) videos on membrane disruption by such antimicrobials and explore how these videos can be analysed and interpreted in terms of fractal formation and/or crack propagation. While this will in first instance involve computational analysis of image data, there may also be scope for gaining involvement in lab-based experiments, depending on students' skills and appetites.

Pattern control during growth: scaling and robustness in developmental networks

Supervisor: Zena Hadjivasiliou | eligible for BioP, Brian Duff and IPLS studentships | can be on campus or online project
The mechanisms that control patterning during growth have the remarkable capacity to adapt, or scale, to the size of a growing tissue. Furthermore, the same mechanisms must mitigate noise to ensure a reproducible and stereotypical organ size and pattern across embryos and adults. It is not immediately obvious whether the mechanisms that mediate scalability and error control are at odds or go hand in hand with one another, and how selection pressures for these features are consolidated during evolution. In this project we will address this question by focusing on morphogen signalling. Morphogens are diffusible molecules that form graded concentration profiles in tissues and control tissue size and patterns. Their profiles often expand as an organ grows and this allows the patterns, they control to remain proportional to the tissue size. As well as being able to scale, morphogen gradients must remain robust to noise. Therefore, cells and tissues must be able to mitigate noise, e.g., due to fluctuations in production at the source, to maintain the correct profile at a given developmental time, while also continuously adapting to changing size. In this project we will build a mathematical model that captures gene interactions known to mediate morphogen scaling to also explore the capacity of these networks to control errors and noise. The framework the student will develop will be placed in an evolutionary context to ask how natural selection can mould the architecture of gene networks to mediate both scalability and control. This project will use PDEs and numerical simulations. 
The proposed project is theoretical although, depending on progress, experimental data may be available to analyse and compare to theoretical predictions. 

Synthesis of Biocompatible Doped and Undoped Iron Oxide Nanocubes for Magnetic Particle Imaging (MPI) and MPI- Magnetic Hyperthermia (MH) Application.

Supervisor: Nguyen Thanh | eligible for BioP, Brian Duff and IPLS studentships | on campus project
Magnetic particle imaging (MPI) is a recently developed tracer-based imaging modality which has emerged as a promising diagnostic and therapeutic tool with wide ranging applications in biomedicine. One such application is MPI in conjugation with MH. MPI-MH offers numerous important advantages over more standard hyperthermia application paradigms, hence our interest. Overall performance of MPI and MPI-MH is almost entirely dependent on the specific magnetic nanoparticle tracers implemented. In this experimental project, you will synthesise high quality doped and undoped cubic iron oxide magnetic nanoparticles through a thermal decomposition technique, optimising them for performance in both MPI, and MPI-MH. Following synthesis, you will completely characterise the physical and magnetic characteristics of the tracers using an array of techniques, including transmission electron microscopy (TEM), x-ray diffraction (XRD), and a superconducting quantum interference device (SQUID). Biocompatibility will be assessed by Dynamic Light Scattering (DLS) and fourier-transform infrared spectroscopy (FT-IR). 

Biocompatibility and colloidal stability of ultra-small IONP as MRI T1 Contrast Agent

Supervisor: Nguyen Thanh | eligible for BioP, Brian Duff and IPLS studentships | on campus project
The current interest for novel positive (T1) contrast agents for magnetic resonance imaging (MRI) arises from the health risks posed by the current clinical gadolinium complexes. Prof. Thanh's group demonstrated that IONPs of ~5 nm (a suitable size for positive T1 MRI contrast agents). In this summer studentship, the student will investigate a colloidal stability of ultra-small IONP, prepared by different syntheses. The student will be tasked with finding an improved surface functionalisation procedure of ultra-small IONP. Building on this, she/he will be asked to devise a best synthetic route for ligand exchange and biostabilisation for obtaining IONP suspensions. Then T1 and T2 relaxation times of the best sample will be tested. 

Characterising diffusible signals for biological spatial computation

Supervisor: Alex Fedorec (Barnes Lab) | eligible for IPLS studentship | on campus project
Synthetic biology has made use of an array of molecules for the control of engineered biological systems. The vast majority of work to date has been performed in liquid cultures in which these molecules are well mixed and therefore at approximately equal concentration throughout the culture. We are working on constructing biological systems which are able to perform computation through the diffusion of signals between spatially patterned, engineered bacteria. In order to predict how the systems that we build will respond, we develop mathematical models. However, a gap in our current understanding of the rates at which the signals diffuse is limiting the accuracy of these models. This project will develop protocols to quantify the diffusion of signalling molecules. Using molecular biology techniques, we will construct engineered strains of bacteria as sensors for the signals. We will use fluorescence imaging and image processing to produce empirical data, and we will use mathematical modelling and computational methods to extract valuable information from the data.

A computational approach to study the role of extracellular matrix (ECM) mechanics in tissue development

Supervisor: Nargess Khalilgharibi (Mao Lab) | eligible for IPLS studentship | on campus project
We will be investigating the role of extracellular matrix (ECM) mechanics in tissue development. The ECM is a protein meshwork that lines most biological tissues, playing important roles in defining tissue shape. Dysregulations in ECM structure and mechanical properties can lead to various developmental defects and disease. While biochemical signalling through ECM has been extensively studied, less is known about the mechanical properties of the ECM and how they contribute to tissue shape. This is due to the fact that conducting mechanical measurements on the ECM is rather challenging experimentally. Therefore, in this project, we will use computational modelling to investigate how different mechanical properties of the ECM affect tissue shape. The project will be hosted in the Mao lab, who have developed a finite element model for this purpose1. The model was originally developed to study tissue folding in the Drosophila wing disc, however, we have now generalised it to make it applicable to a variety of tissues and multicellular systems (e.g. organoids). The student will be working with this model, running simulations with different configurations and testing the new features of the model. In particular, we would like to test the model’s applicability to organoid systems. The student will be using core practices for good software development (version control, automating, testing, documentation), all of which are vital for any career involving computational coding.
1Tozluoǧlu, M. et al. Planar Differential Growth Rates Initiate Precise Fold Positions in Complex Epithelia. Developmental Cell 51, 299-312.e294, doi:https://doi.org/10.1016/j.devcel.2019.09.009 (2019).

Multiscale modelling of living matter

Supervisor: Philip Pearce | eligible for IPLS studentship | can be on campus or online project
The properties and dynamics of biological tissues, organisms and populations emerge from physical and chemical interactions at the levels of molecules and cells. This project can focus on any of these length scales, and can involve a computational or analytical approach. Example projects include: simulating interactions between extracellular matrix proteins in bacterial biofilms; simulating cell populations at the cellular level; or modelling bacterial populations or tissues using a continuum approach.