Jobs and PhDs
(MRC DTP) GlycoTryps: Investigating The Role of the Glycocalyx in mediating host-pathogen interactions and tissue immunity, University of Manchester
African trypanosomes are the causative agents of devastating diseases of medical and veterinary importance, including sleeping sickness in humans and extreme wasting disease in animals in Sub-Saharan Africa. Conservative estimates suggest that over 20 million people are currently at risk of infection. Furthermore, this infection also has a massive economic impact on agriculture leading to the loss of ~ 20 billion dollars per year in cattle stock. Our recent work has shown that localised immune responses are essential to drive the various arms of the pathology in both mice and humans, but the mechanisms that kickstart these processes are not understood.
In order to induce such devastating effects on the host, African trypanosomes first need to overcome the critical barrier imposed by the vasculature, which is characterised by having a rich and dense surface glycocalyx. The endothelial surface glycocalyx is an understudied structure composed of glycoproteins (primarily proteoglycans) and glycolipids, and is present on a range of cells including the endothelium and macrophages. We hypothesise that the interaction between African trypanosomes with the endothelial glycocalyx has profound implications for tissue immunity and pathology. In this context, the endothelial glycocalyx becomes the ultimate physical site dictating host-pathogen interactions and downstream tissue responses.
Progress in understanding the glycocalyx function in biology has been hampered by the lack of established techniques to study it experimentally. This project will determine for the first time the role of the endothelial and leukocyte glycocalyx in the local immune responses against African trypanosomes in tissues critical for disease transmission (skin, adipose tissue) and pathology (brain and brain borders) by establishing a range of cutting edge techniques.
We will analyse and compare the glycocalyx across tissue sites and time points of infection using multiplex imaging to understand the spatial distribution of African trypanosomes in relation to points of leukocyte extravasation and tissue entry. We will also determine the mechanisms that mediate trypanosome-glycocalyx interaction using cutting-edge 3-dimensional tissue imaging (e.g., lightsheet microscopy, electron tomography) and genome-wide screening to define the nature of the niches formed between parasites and glycocalyx niches, as well as to identify parasite-specific components essential for such processes. By manipulating the glycocalyx of immune and endothelial cells in various models of infection, we will demonstrate for the first time the functional relevance of the glycocalyx in mediating host-pathogen interactions, providing unparalleled insights into how these important aspects dictate tissue responses to infection.
https://research.manchester.ac.uk/en/persons/juan-quintana
https://research.manchester.ac.uk/en/persons/matthew-sinton
https://research.manchester.ac.uk/en/persons/douglas.dyer
Eligibility
Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How to Apply
To be considered for this project you MUST submit a formal online application form – on the application form you must select MRC DTP PhD Programme. If you select the incorrect programme your application cannot be considered. Full details on how to apply can be found on the MRC DTP website.
Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application, please contact our admissions team.
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website.
Studentship funding is for 4 years and covers tuition fees and an annual stipend. This does not include any costs associated with relocation.
Postdoc, Smith College
The Department of Biological Sciences at Smith College invites applications for a benefits eligible postdoctoral position, focusing on genome evolution in microeukaryotes (aka protists), to begin on or after December 1, 2024. The bulk of the work will focus on bioinformatic analyses of data generated in the lab from diverse amoebae. The initial appointment is for one year, with the possibility of extending for additional years. The position will be housed in Professor Laura Katz's laboratory in the Department of Biological Sciences ; questions should be directed to lkatz@smith.edu.
The goals of this research include characterizing genome architecture in poorly-studied clades and reconstructing the evolutionary history of both genes and species (i.e. species delimitation). The ideal candidate will: 1) be a productive researcher with interests in both biodiversity and phylogenomics of microorganisms; 2) have experience identifying and isolating diverse protists; 3) have knowledge of bioinformatic and/or phylogenetic tools; 3) have excellent communication and interpersonal skills; and 4) be interested in collaborating with graduate and undergraduate students in the laboratory.
Research in the Katz lab aims to elucidate principles of the evolution in eukaryotes through analyses of microbial groups, and to assess how these principles apply (or fail to apply) to other organisms. Currently we focus on three interrelated areas: (1) characterizing evolutionary relationships among eukaryotes using single-cell ‘omics’ and phylogenomics; (2) exploring the evolution of germline vs somatic genomes; and (3) describing the phylogeography and biodiversity of protists in local environments (bogs, fens, coastal habitats).
Located in Northampton, MA, Smith College is the largest women’s college in the country and is dedicated to excellence in teaching and research across the liberal arts. The College is a member of the Five College Consortium with Amherst, Hampshire and Mt. Holyoke Colleges, and the University of Massachusetts Amherst and students cross-enroll and faculty cross-teach across the Five Colleges.
Submit application through Smith’s employment website with a cover letter, curriculum vitae, sample publications and the contact information for three confidential references. Finalists may be asked for additional materials. Review of applications will begin on September 18, 2024.
Position Title: Postdoctoral Researcher Location: Montpellier France
