PROJECT CODE*

SUPERVISOR

PROJECT TITLE

PROJECT DESCRIPTION

LB**

RESEARCH GROUP/PI WEBSITE

P01

Miguel A. Valvano

1. valvano@qub.ac.uk
2. brazil@qub.ac.uk

Exploring mechanisms of resistance to last-resort antibiotics

Antibiotics are the greatest success story of modern medicine, but the steady global increase of infections caused by multidrug antibiotic resistant (AMR) bacteria has turned into one of the greatest threats to human health. The aim of this project is to investigate the mechanisms of resistance in AMR Enterobacter cloacae complex isolates by: (1) testing the virulence potential of the Enterobacter cloacae complex isolates in the Galleria mellonella moth larvae infection model; (2) conducting qRT-PCR assays comparing the expression of selective colistin resistance associated genes and potential regulators in pre- and post-infection isolates. Enterobacter species can become resistant to Colistin, a last resort antibiotic, either by the horizontal transfer of modifying genes or by the expression of heteroresistance in the bacterial population; and (3) comparing the lipid A profile of colistin-sensitive and colistin-resistant isolates.
At a minimum, the student will learn general microbiology and molecular biology techniques, PCR amplification, infection model in Galleria mellonella, and rudiments of mass spectrometry. General techniques of biochemistry and molecular biology will be applied, as well as a rigorous hypothesis-driven thinking process to learn scientific method along the way. The student will join a highly accomplished research team environment. The student should work hard and be prepared to learn and apply experimental design as well as execute the required experiments with technical proficiency. Attendance and presentation of ongoing research at weekly lab meetings is mandatory, as well as to weekly individual meetings with Dr. Valvano to assess progress. It is highly advisable that students consult http://publish.uwo.ca/~mvalvano/ or email to m.valvano@qub.ac.uk. for additional information and to familiarize with the Valvano Lab ethos.

YES

https://publish.uwo.ca/~mvalvano/

P02

Derek Brazil

Unravelling the mechanisms of Gremlin1 signaling in colorectal cancer and kidney fibrosis

We work on Gremlin1, a secreted protein antagonist that inhibits bone morphogenetic protein signaling in a range of cells. Levels of Grem1 are high in many diseases, including fibrosis of the kidney, liver and lungs. High levels of Grem1 are associated with poor patient prognosis. Grem1 therefore represents an attractive novel drug target, and we have developed novel small molecule inhibitors of Grem1 as new drug candidates.
This project will involve the student deciphering Grem1 signaling using a range of cell culture models. Methods such as Western blotting, ELISA and fluorescence microscopy will be used during the project. The student will be exposed to cutting-edge molecular cell biology research in the Brazil laboratory and will be part of a dynamic research team advancing our understanding and treatment of human cancer and kidney disease. Previous summer students in the Brazil laboratory have been included as co-authors on research publications. 

NO

https://www.qub.ac.uk/schools/mdbs/Research/find-a-phd-supervisor/dr-derek-brazil.html;

 https://pure.qub.ac.uk/en/persons/derek-brazil

P03

Dessi Malinova

d.malinova@qub.ac.uk

B cell polarity and antigen endocytosis

We are interested in B cell antigen uptake, a process crucial for B cell proliferation, differentiation and production of high-affinity antibodies. We recently identified Endophilin as a regulator of antigen endocytosis in B cells. Endophilin was shown to specifically localise to the leading edge of adherent cells, and interact with cell polarity regulators during angiogenesis. The process is uncharacterised in B cells and we would like to understand how cell polarity regulators and organelles are organised in the presence or absence of endophilin. In preliminary data, endophilin knockout cells exhibit disrupted alpha-tubulin organisation upon antigen activation implicating a link with the cytoskeleton. We will delete candidate genes in B cells and quantify polarisation of cytoskeleton, integrins and organelles. The research will involve molecular biology, including CRISPR-mediated gene deletion, cell culture, flow cytometry and imaging, giving the candidate experience in a wide range of techniques used in immunology and cell biology.

YES

https://www.malinovalab.com/

P04

Guilherme Costa

g.costa@qub.ac.uk

How do RNA-binding proteins shape blood vessels?

The vasculature is comprised of a complex network of blood vessels responsible for the vital distribution of supplies to the tissues. Although the vasculature is the first organ to form, the continued changes in supply demands induce growth of the vessel network throughout life. In particular pathological conditions, such as cancer and diabetes, the dysregulation of vessel formation results in dysfunctional vasculature with critical consequences for tissue health. Hence, understanding how new blood vessels form is key to tackle such diseases. This project aims to study RNA-binding proteins (RBPs) in vascular cells and how they regulate vessel formation. To do so, the student will use a fascinating toolbox of techniques that allow the subcellular visualisation of RNAs and RBPs. The student will have the opportunity to be directly trained by the PI and will gain state-of-the-art skills in cell culture, molecular and cell biology, microscopy and statistical analysis.

YES

https://pure.qub.ac.uk/en/persons/guilherme-costa

P05

Gunnar Schroeder

1. schroeder@qub.ac.uk
2. coll@qub.ac.uk

Identification of virulence factors of intracellular bacterial pathogens

Bacterial pathogens secrete protein virulence factors to manipulate host cells. Deciphering the function of these is critical to understand pathogenesis and develop new treatments. In this project you will delete new putative virulence factors, which we identified in pathogenic Legionella species, from the bacteria and assess the effect on the competitiveness of the strains in infection assays. You will learn a wide range of molecular biology skills such as cloning, chromosomal deletion as well as handling of non-pathogenic and pathogenic bacteria and infection assays.

YES

https://pure.qub.ac.uk/en/persons/gunnar-neels-schroeder

P06

Rebecca Coll

Evaluation of small molecules as modulators of the NLRP3 inflammasome

Inflammasomes are intracellular protein complexes that form part of the innate immune response to infection and injury. Inflammasomes trigger the secretion of inflammatory cytokines (IL-1beta) and cell death (pyroptosis). Excessive activation of the NLRP3 inflammasome is associated with many diseases including Alzheimer’s, Parkinson’s, atherosclerosis, liver disease, and asthma. Molecules that inhibit or modify NLRP3 can potentially be developed as therapies for these conditions. In this project we will evaluate the effects of various small molecules (e.g. heat shock protein inhibitors and kinase inhibitors) on inflammasome activation.

The student will test molecules in a mouse macrophages stimulated with NLRP3 activators (e.g. lipopolysaccharide and nigericin). They will measure inflammasome activation using assays for cell death, IL-1beta secretion, and by Western blotting for IL-1beta processing, caspase-1 activation, and ASC-speck formation. Inhibitor specificity will be evaluated by testing responses to AIM2 inflammasome stimulation and by measuring TLR-dependent cytokine secretion.

YES

https://pure.qub.ac.uk/en/persons/rebecca-coll

P07

David Courtney

1. courtney@qub.ac.uk

Visualising the RNA of influenza A virus in infected human cells.

Influenza A virus is an important respiratory pathogen, having caused 6 major pandemics over the last 130 years and results in innumerable deaths every winter. This project aims to develop a method of visualising individual influenza A virus RNA in an infected cell. This method will then be used to determine how alterations in the levels of host proteins can affect viral RNA trafficking. This project will use recently published techniques such as HALO and SNAP protein tags in a novel way, and will generate useful data that will contribute to ongoing research within the group. This exciting project would be perfect for a student interested in virology and molecular biology, and will provide the successful student with skills in molecular biology, virology and fluorescent microscopy.

YES

davidgcourtney.com

P08

Eleni Beli

1. beli@qub.ac.uk
2. lois@qub.ac.uk

Disruption of circadian retina function in diabetes

We have gathered preliminary data that indicates circadian disruption of photoreceptor function in type 1 diabetes. The disruption was mostly found in the second order neurons of the retina. Thus, in this project the student will perform immunofluorescence for inner nuclear neurons (bipolar, amacrine cells) in retinas collected at different times of the 24hr cycle to identify whether the locations and connections of the inner neurons is affected by diabetes.
The student will learn basic tissue histology techniques (parafin sectioning, immunostaining, imaging and analysis) that are applicable to the wider medical field.
 

YES

https://pure.qub.ac.uk/en/persons/eleni-beli

P09

Professor Noemi Lois

Concordance between eyes of phenotypic features of Diabetic Retinopathy

Diabetic retinopathy (DR) is categorised into stages based on severity of retinal lesions.  A variety of features can be observed in people with DR, predominantly due to the development of retinal ischaemia, including microaneurisms, intraretinal haemorrhages, cotton wool spots, hard exudation, venous beading, intraretinal microvascular abnormalities and new vessels.  As DR is a systemic disease resulting from long-term hyperglycaemia, it could be hypothesised that it would affect both eyes relatively symmetrically.  If this were not to be observed, it would suggest that local eye factors and/or specific individual eye characteristics may modulate the disease.

This project involves undertaking a review of the literature to synthesise data on concordance between eyes of features of DR.  The student will gain knowledge and experience in DR, on the undertaking of systematic searches of electronic medical databases, identification of eligible studies, on data collection, statistical analysis, interpretation of results, and skills on academic writing.

NO

https://pure.qub.ac.uk/en/persons/noemi-lois

P10

Bettina Schock

1. schock@qub.ac.uk
2. fitzgerald@qub.ac.uk

Characterization of stimulated iPSc derived fibroblasts

Fibroblast proliferation into myofibroblasts contributes to the development of fibrotic lung disease. However, to study the contribution fibroblasts play in the development of such diseases is hampered by the lack of accessibility of disease fibroblasts. We have set up a model system using iPSC-derived fibroblasts. In this project we want to characterize these fibroblasts and compare their activation with lung derived fibroblasts.
In this project, fibroblasts (iPSC derived and normal lung fibroblasts stimulated with TGFbeta) will be characterised for activation markers using Western blotting.

YES

https://pure.qub.ac.uk/en/persons/bettina-schock

P11

Denise Fitzgerald and Jessica White

 jwhite51@qub.ac.uk

How do T cells help repair the brain?

Oligodendrocytes produce myelin that insulates axons in the central nervous system, providing metabolic support and accelerating nerve signals. In multiple sclerosis, myelin sheaths on axons are damaged (demyelination). In response, oligodendrocyte progenitor cells (OPCs) migrate to the site of damage, proliferate, differentiate into mature oligodendrocytes, and carry out the regenerative process known as remyelination. Unfortunately, this is not always successful, resulting in a lack of functional recovery and subsequent disease progression. Research has shown that immune signalling is important in remyelination, and recently our group has shown that regulatory T cells (Tregs) are required for successful myelin repair (Dombrowski et al. Nature Neuro, 2017). This project aims to investigate mechanisms of how Treg drive OPC differentiation and remyelination. The student will learn molecular biology techniques, immunohistochemistry, microscopy, and possibly bioinformatics and tissue culture.

YES

https://www.facebook.com/TheFitzgeraldGroup1 

https://pure.qub.ac.uk/en/persons/denise-fitzgerald

P12

Judy Bradley

1. bradley@qub.ac.uk

Supporting stakeholder Engagement within NI clinical trial infrastructure: IREACH  

This is an exciting opportunity for a student to work with the IREACH team. IREACH (Institute of Research Excellence for advanced Clinical Healthcare) aims to provide a unified capability for clinical trials within the Belfast region and beyond. Central to delivering this ambition is stakeholder engagement: patients; public; clinicians; industry. The student will join one of these stakeholder workstreams to seeks views on the development of aspects of IREACH e.g. the build; processes for research setup and delivery; creating opportunities and efficiencies.
The successful student will gain experience of using a range of methods e.g. interviews; surveys; questionnaires to gather information and will analyze this information to inform decision making within IREACH. They will have opportunity to network with leaders across the research infrastructure. They will gain insight into processes within clinical trials and clinical trial service delivery. 

 NO

 https://pure.qub.ac.uk/en/persons/judy-bradley