Understanding the genetics and function of complex human retinal phenotypes

The human retina is the tissue at the back of the eye responsible for converting light stimulus into neuronal signal that can be interpreted by the brain. To perform this integral role within the central nervous system, the retina has a complex and layered structure, with each layer performing a vital step in the signal transformation process. Changes in the morphology of this structure are often a consequence of disease, which can affect the function of the eye. Better understanding of the genetics influencing this structure may teach us about the biological processes underlying these diseases as well as general eye development. The retina is imaged routinely in the clinic using optical coherence tomography (OCT), providing a non-invasive imaging technique that produces high-resolution, three-dimensional representations of the retina from which measures describing retinal morphology can be extracted. This thesis summarises my research into the genetic variation underlying retinal morphology. Firstly, I explored the morphology of the inner retina, whose thickness is used as a biomarker of glaucoma, using quantitative phenotypes extracted from OCT. I conducted genome-wide association studies (GWAS) of the thickness of the retinal nerve fibre layer and the ganglion cell inner plexiform layer to understand the genetic variation driving inner retinal morphology. I further explored the causal relationship between the inner retina and glaucoma using Mendelian randomisation analysis. I next performed GWAS of the thickness of the outer retinal layers, including both the component photoreceptor cell layers (the outer nuclear layer, inner segment, and outer segment), and the retinal pigment epithelium layer. I explored how genetic variation was affecting the outer retinal morphology at a higher dimension by looking for genetic variants that were differentially affecting the outer retinal thickness at the central macula compared to the peripheral macula. To further explore the rich dimensionality of OCT data, I developed several image analysis techniques to gain more granular information about the morphological variation being affected by the discovered genetic variants. In doing so I established a novel population level trait and examined its effect on visual acuity. In summary, this thesis provides a well-rounded and detailed look into the genetic variation underlying morphological variation of the retinal layers. As the largest study of retinal layer genetics of its kind, it offers insight into clinical ophthalmology and retinal development, and furthermore opens new avenues for clinical research.Funding was provided via the EMBL international PhD programme

A consensus of playwriting theory

Call number: LD2668 .T4 1985 C87Master of Art

FFPred 3: feature-based function prediction for all Gene Ontology domains

Predicting protein function has been a major goal of bioinformatics for several decades, and it has gained fresh momentum thanks to recent community-wide blind tests aimed at benchmarking available tools on a genomic scale. Sequence-based predictors, especially those performing homology-based transfers, remain the most popular but increasing understanding of their limitations has stimulated the development of complementary approaches, which mostly exploit machine learning. Here we present FFPred 3, which is intended for assigning Gene Ontology terms to human protein chains, when homology with characterized proteins can provide little aid. Predictions are made by scanning the input sequences against an array of Support Vector Machines (SVMs), each examining the relationship between protein function and biophysical attributes describing secondary structure, transmembrane helices, intrinsically disordered regions, signal peptides and other motifs. This update features a larger SVM library that extends its coverage to the cellular component sub-ontology for the first time, prompted by the establishment of a dedicated evaluation category within the Critical Assessment of Functional Annotation. The effectiveness of this approach is demonstrated through benchmarking experiments, and its usefulness is illustrated by analysing the potential functional consequences of alternative splicing in human and their relationship to patterns of biological features

MLCut : exploring Multi-Level Cuts in dendrograms for biological data

Choosing a single similarity threshold for cutting dendrograms is not sufficient for performing hierarchical clustering analysis of heterogeneous data sets. In addition, alternative automated or semi-automated methods that cut dendrograms in multiple levels make assumptions about the data in hand. In an attempt to help the user to find patterns in the data and resolve ambiguities in cluster assignments, we developed MLCut: a tool that provides visual support for exploring dendrograms of heterogeneous data sets in different levels of detail. The interactive exploration of the dendrogram is coordinated with a representation of the original data, shown as parallel coordinates. The tool supports three analysis steps. Firstly, a single-height similarity threshold can be applied using a dynamic slider to identify the main clusters. Secondly, a distinctiveness threshold can be applied using a second dynamic slider to identify “weak-edges” that indicate heterogeneity within clusters. Thirdly, the user can drill-down to further explore the dendrogram structure - always in relation to the original data - and cut the branches of the tree at multiple levels. Interactive drill-down is supported using mouse events such as hovering, pointing and clicking on elements of the dendrogram. Two prototypes of this tool have been developed in collaboration with a group of biologists for analysing their own data sets. We found that enabling the users to cut the tree at multiple levels, while viewing the effect in the original data, isa promising method for clustering which could lead to scientific discoveries.Postprin

Once upon a time: Designing a narrative-inspired curriculum for a Postgraduate Certificate in Teaching in Higher Education

Once upon a time, there was a group of old teachers (well, maybe not so old, thanks very much) whose job it was to help other people learn to teach. They had high satisfaction with their jobs (as everyone in HE seems to have nowadays) and they liked the new teachers they worked with. Most of the new teachers seemed to find the old teachers useful, and they went out into the world with good ideas about how to teach. But something was troubling the old teachers. Some of the new teachers were finding it difficult to use the reflecting pool to think about their teaching. Some of them were scared to look into the pool afraid of what they might see, while others preferred to copy how teaching was done around them and did not want to use the pool at all. The old teachers scratched their heads, and had meetings where they argued about different ideas, and eventually they had a solution: they would tell the new teachers lots of stories, about themselves and about teaching, and encourage the new teachers in turn to tell stories. They wrote a big book (well a modest Moodle book called the ‘Module Anthology’) about teaching, with a chapter devoted to each of the main aspects of teaching, and in each chapter they encouraged the new teachers to use the reflecting pool and to tell their own stories. Did they live happily ever after? We don’t know yet, but we’re starting to think that maybe they did..

Rethinking Assessment? Research into the the affective impact of higher education grading

Assessment plays a central role in learning in higher education (HE), but often the impact of grading assessment on student motivation, behaviour and wellbeing is insufficiently considered in policy and practice. With the growing concern in the HE sector about student mental health, a consideration of the affective dimension of grading is timely. The discussion in this paper on the affective dimension of grading is based on research conducted during the pandemic on the no-detriment implementation of pass/fail assessment at the University of the Arts London (UAL). Qualitative research was undertaken with first-and second-year undergraduate students in the fields of creative arts, design and communication to investigate the effects of the switch from letter grading to pass/fail and student views on grading more generally. Our findings suggest that grading affects student stress, anxiety, learner identity, motivation, student self-expression, creativity, and peer relationships. In the light of our findings, we bring together discourses about assessment, grading and student wellbeing to consider the longer-term implications for assessment practices in a post-pandemic world

Belonging through Assessment: Pipelines of Compassion

This paper presents the QAA Collaborative Enhancement Project 2021 - Belonging through assessment: Pipelines of compassion. The project is a collaboration between University of the Arts London, Glasgow School of Art, and Leeds Arts University. The project began against the backdrop of pandemic and the team identified a shift in assessment practices across the three participating arts institutions and address social justice, belonging and inclusion through compassion. The project aims to: • Identify areas of enhancement in assessment policies and practices to promote student sense of belonging and tackle issues of social justice. • Link this relational work with attainment gap/awarding differentials agendas in the creative arts. • Develop collaborative, dialogic, polyvocal and affective resources for staff development across the HE sector. The three research strands: 1. Pass/fail grading 2. Whole self: trauma-informed policies 3. Feedback (compassion and emotional impact) Drawing on these strands, we share our research and resources to help universities reflect on their assessment policies and practices. We offer approaches to design these with compassion to meet students where they are at. Ultimately, these principles can be used to develop student belonging and more culturally responsive education in the creative arts

Designing Eportfolio Based Learning Activities to Promote Learner Autonomy

YesThis report is a summary of the activity and findings of a small-scale educational research project conducted as the part of the Fourth Cohort of the Inter/National Coalition for Research into Electronic Portfolios. The project was conducted between 2007 and 2010 at the University of Bradford in the UK. It investigates how academic staff are utilising eportfolio tools to support learner development, particularly within specific modules of study. In particular it aims to identify strategies that contribute to the development of learner autonomy. Modules from a range of subject areas: Psychology, Midwifery, Geography and Combined Studies were included in the study