Host: Prof Liz Miller

Venue: MSI Small Lecture Theatre, SLS

Abstract

The choroid plexus (ChP) is a highly secretory tissue and an important signalling centre located in our brain. This tissue displays a number of important functions such as forming a protective epithelial barrier and secreting the cerebrospinal fluid (CSF). The CSF is important for the maintenance of physiological levels of nutrients in the brain, for the transport of signalling molecules and growth factors and for its protective role in the regulation of intracranial pressure. Most of the studies about the ChP have been conducted in rodents or 2D models, which don’t fully recapitulate the complexity of human ChP. To explore the role of the ChP-CSF system, we recently established a protocol to generate human ChP organoids using a combination of signalling molecules that are physiologically present during the stages of development of this tissue. These organoids recapitulate fundamental functions of ChP such as CSF secretion and formation of a tight epithelial barrier selectively permeable to small molecules. Combining single-cell RNA-sequencing with immunohistochemical and EM validation, we detected the presence of ChP specific channels and transporters localised on the apical brush border of the ChP epithelium. We are now examining the temporal development and maturation of these organoids. We found that, like ChP tissue in vivo, organoids stop proliferating in vitro and develop features of a mature tissue. Recently, we used this model to study kinetics of CSF secretion in vitro and explore disease-biomarkers that could be relevant for conditions such as normal pressure hydrocephalus. In conclusion, ChP organoids have been proven useful in multiple applications and represent a powerful tool to study not only developmental diseases but also conditions affecting adult human ChP.

Host: Professor Claire Halpin

Venue: MSI Large Lecture Theatre, SLS

Biography:

Professor Muir is a chemical biologist known for his contributions to the fields of peptide and protein chemistry. Chemistry-driven technologies developed in his group open up the world of proteins to the tools of organic chemistry by allowing the incorporation of non-coded elements including unnatural amino acids, posttranslational modifications and isotopic probes site-specifically into proteins. These approaches are now widely employed in academia and industry. His current research interests lie principally in the area of epigenetics, where he uses chemical biology approaches to illuminate how chemical changes to chromatin are linked to different cellular phenotypes.

Host: Dr Helge Dormueller

Venue: Sir Kenneth & Lady Noreen Murray Seminar Room, CTIR 2.84

Abstract  

Dr Kelly is an Assistant Professor in the Department of Applied Sciences at Northumbria University, Newcastle. His research group focusses on developing solutions to some key limitations encountered in Engineering Biology and Biotechnology. This talk will discuss some of the ongoing projects in the group including: (1) the rapid screening of synthetic small RNAs to combat antibiotic resistance; (2) how best to produce complex metabolic pathways in heterologous hosts with many cofactor-containing enzymes so they scale up from lab to industrial applications; and (3) approaches to evolving an agriculturally-important plant growth-promoting soil bacterium for fundamental plant-microbe interaction studies, as well as for use in commercial agriculture. 

Dr Xiaocheng Shang will discuss the design of state-of-the-art numerical methods for sampling probability measures in high dimension where the underlying model is only approximately identified with a gradient system. Extended stochastic dynamical methods, known as adaptive thermostats that automatically correct thermodynamic averages using a negative feedback loop, are discussed which have application to molecular dynamics and Bayesian sampling techniques arising in emerging machine learning applications. 

Dr Xiaocheng Shang will also discuss the characteristics of different algorithms, including the convergence of averages and the accuracy of numerical discretizations.

Venue: Fulton Building, Room G20

Experimental brain activity is known to show oscillations in specific frequency bands, which reflects neural information processing. For instance, strong oscillations at about 2Hz reflect tiredness and sleepiness, strong 40Hz oscillations indicate alertness. Changes of power in frequency bands indicate changes in information processing. For instance, it has been observed that strong activity about 10Hz and 2Hz emerge in electroencephalographic activity (EEG) when a subject loses consciousness in general anaesthesia. Numerical simulations of stochastic neural models have shown that such a change can be reproduced by changing the variance of external additive Gaussian uncorrelated noise. At a first glance, this is surprising since additive is not supposed to affect a system’s oscillatory activity or stability.

The presentation shows first how additive noise can affect a nonlinear system’s stability by applying stochastic center manifold analysis in non-delayed low-dimensional systems and delayed systems. Then, an extension to stochastic randomly connected network models shows that the observed effect also emerges in networks. Applying random matrix theory together with mean-field theory demonstrates how additive noise tunes the stability and oscillatory activity in such systems. In sum, the mathematical studies provide an explanation why the brain’s oscillatory activity changes with changing experimental conditions.

Venue: Fulton Building, Room G20

The physical processes controlling mixing in the uppermost layer of the ocean are still poorly understood. Although this part of the water column is often weakly stratified due to direct solar heating or air bubble entrainment, the possible role of weak stratification has never been considered and was a priori generally believed to be negligible. Here, aiming at getting an insight into mixing mechanisms in the oceanic surface boundary layer we develop a weakly-nonlinear asymptotic model of nonlinear dynamics of linearly decaying three-dimensional long-wave perturbations in a generic no-stress weakly stratified boundary-layer flow. 

The perturbation evolution is shown to be described by a novel generalization of the essentially two-dimensional Benjamin-Ono equation modified by the explicit account of linear viscous decay and weak stratification. Within the framework of the new evolution equation an initial localized perturbation (`lump') of any given shape collapses, i.e., forms a point singularity in finite time, provided its initial amplitude exceeds a certain threshold specific for each particular initial shape, the Reynolds number, stratification, and the curvature of the basic flow vorticity at the boundary. 

For a broad range of Reynolds numbers where the linear decay is negligible the sufficient criterion for collapse has been found in a compact analytical form. The system has two attractors: the collapse and unperturbed flow; the initial perturbations exceeding the threshold collapse in a self-similar manner, while the perturbations with the amplitudes below the threshold - decay. The weak stratification and decay strongly affect the threshold. Although weak stratification does not affect linear stability properties of the flow, it might raise the threshold beyond the range of validity of weakly nonlinear model. We find the self-similar solution describing the collapses in the vicinity of the singularity. 

The axially symmetric solution is universal: it does not depend on the account of stratification and linear decay. Collapses are suggested as a mechanism resulting in coherent three-dimensional coherent structures and enhancement of mixing in linearly stable boundary layers.

Venue: Fulton Building, Room G20

An attractive approach to tackling the complexity of a turbulent fluid flow is to view the behaviour from a dynamical systems perspective. That is, we might imagine a trajectory navigating a high dimensional phase space directed by the stable and unstable manifolds of simple invariant states. In a fluid system such invariant states might take the form of steady equilibria, travelling waves or time periodic orbits. In many cases isolating such states is challenging due to their high instability. 

In this talk we will introduce the method of “time-delayed feedback control” as a method to passively stabilise travelling wave solutions to the Navier-Stokes equations. We will survey recent results in this project where we successfully stabilise states from two-dimensional turbulence and turbulence in a rectilinear periodic pipe. 

In both cases travelling waves can be stabilised at relatively large Reynolds numbers, and in each situation we outline some novel approaches to improve the performance of the control. Along the way we perform linear stability analyses and use methods from control theory to validate our results and help us gain additional insight into the mechanisms underpinning successful control. 

We also demonstrate gradient descent methods to help optimise control parameters to avoid laborious searching and enable states to be obtained from speculative guesses.

Venue: Fulton Building, Room G20