PhD opportunity

This page is to showcase the Omics-related PhD projects in the University of Leeds

 

Title: How do RNA structures in the Chiikungunya virus genome control replication in human and mosquito host cells?

Project description: Chikungunya virus is a mosquito-transmitted arbovirus that re-emerged as an epidemic in 2005 around the Indian Ocean, before spreading across Asia, Africa, Europe and the Americas. It continues to spread across regions harbouring its mosquito vector – including much of North America and Western Europe. Chikungunya virus causes acute ‘Dengue or Zika like’ symptoms and chronic, debilitating musculoskeletal pain with neurological complications.
We recently published a study (Kendall et al., 2019 NAR) identifying novel structural elements within the RNA genome of Chikungunya virus. While the RNA structures are essential for efficient replication of the virus genome, evidence suggests that they are under different selection pressures in their human and mosquito host-cells. This project will use cutting edge molecular virology, genomics and structural methods to investigate mechanisms by which RNA structure in the Chikungunya virus genome functions in human and mosquito host cells.
There are no vaccines or antiviral therapies for Chikungunya virus. The longer-term goal of our research is to provide greater understanding of the virus replication cycle – in order to develop attenuated vaccines and novel antiviral targets. As part of the Tuplin group you will trained within an active cross-disciplinary research environment.

Omics component: (1) RNAseq analysis of stem-loop mutant virus escape mutants in vertebrate and invertebrate host cells. (2) Analysis of RNA viral RNA structure using SHAPE.

Contact person: Andrew Tuplin (a.k.tuplin@leeds.ac.uk)

Deadline: January 6th 2020

findaphd link

Title: Control and inhibition of virus replication

Project description: The Tuplin laboratory utilises a range of cutting-edge approaches to investigate how arboviruses – specificaly Chikungunya, Dengue and Zika viruses – control replication and translation of their genomes through interactions between RNA structures, host cell proteins and non-coding RNA, and the potential of such RNA elements/interactions as novel therapeutic targets.

You will be involved in a highly novel project which utilises a multidisiplinary approach and cutting-edge methodology – combining molecular virology, genomics, quantitative proteomics, structural biology, imaging, cell biology and structural-based rational drug design. Consequently, you will gain experience across wide range of molecular biology, cell culture and virological techniques.

Omics component: (1) RNAseq analysis of stem-loop mutant virus escape mutants in vertebrate and invertebrate host cells. (2) Analysis of RNA viral RNA structure using SHAPE. (3) Quantitative proteomic analysis of RNA stem-loop/protein interaction using Tandem Mass Tagging.

Contact person: Andrew Tuplin (a.k.tuplin@leeds.ac.uk)

Deadline: Applications accepted all year round – self funding students only

findaphd link

Title: Characterisation of sequence-dependent phosphohistidine phosphatases

Project description: Phosphohistidine is an ubiquitous modification in bacterial cell signaling, however its function in eukaryotic cells has not been defined. In this project, you will combine the use of existing chemical tools with chemical proteomics, biophysics and structural biology to characterize the interaction of known phosphohistidine modifying proteins with their substrates and to identify candidate proteins in human cells capable of acting to controllably remove the modification. The project would suit either a biochemistry or chemistry graduate with an interest in exploring the chemistry/biology interface.

Omics component: This project will use proteomic methodologies to characterise the interactions of chemical tools mimicking phosphohistidine-containing peptides with proteins.

Contact person: Dr. Megan Wright (m.h.wright@leeds.ac.uk)

Deadline: 6th January 2020

findaphd link

Title: Role of RNA modifications in virus infection

Project description: The human tumour virus, Kaposi’s sarcoma-associated herpesvirus is the cause of the most common HIV-associated cancer in Africa, Kaposi’s sarcoma, and two other lymphoproliferative diseases. We have recently shown that KSHV-encoded RNAs are heavily m6A modified and that the modification of host cell RNAs is drastically altered during infection (Baquero et al., (2019) eLife, 8:e47261). This project now aims to determine how and why KSHV manipulates the host cell RNA modification machinery. Specifically, we aim to address the key question of why the m6A modification status of host cell RNAs are altered and how this enhances KSHV replication. This may provide new avenues to antiviral strategies for this important human pathogen of global importance.

Omics component: This project can only be achieved using an interdisciplinary approach, using molecular virology and cell biology, coupled with CLIP-seq analysis and NGS transcriptomic analysis and bioinformatic approaches to analyse transcriptome and data and quantitative skills to analyse differential expression patterns.

Contact person: Professor Ade Whitehouse (a.whitehouse@leeds.ac.uk)

Deadline: 6thJanuary, 2020

findaphd link

Title: Role of m6A reader proteins in virus infection

Project description: Emerging evidence suggests that modifications on RNAs can regulate multiple RNA processing events and therefore control gene expression. The most common RNA modification is m6A methylation. m6A functions by recruiting m6A reader proteins directly to methylated RNAs, once bound the reader proteins then dictate the fate of the RNA. We have recently shown that viruses manipulate the host cell m6A machinery enhancing their own replication (Baquero et al., 2019, eLife 8:e47261). We have identified a novel group of m6A reader proteins that specifically recognize viral methylated RNAs. This project will now address how these novel reader proteins preferentially recognize the viral methylated transcripts over cellular methylated transcripts. We hypothesize that viral methylated RNAs contain additional sequence or structural elements which confer m6A reader protein recruitment and specificity.

Omics component: We will utilize a range of cutting edge techniques, such as RIP-seq and in-cell Shape mapping, to identify these sequence motifs or structural elements.

Contact person: Professor Ade Whitehouse (a.whitehouse@leeds.ac.uk)

Deadline: 6thJanuary, 2020

findaphd link

Title: Novel Gene-Diet Interactions and Determinants of Health in High-Risk Minority Groups

Contact person: Michael A. Zulyniak (M.A.Zulyniak@leeds.ac.uk)

Deadline: Friday, March 29, 2019

findaphd link

Title: Understanding cellular signaling networks via protein-conjugated chemical tools

Project description: Proteins form spatially organized, dynamic complexes in cells, giving rise to signalling networks essential for maintaining cellular function. In this project, you will develop new tools for directly labelling proteins in their native cellular environment. Our approach uses Affimers (small antibody alternatives) to direct the transfer of labels from a chemical tool to a target protein. You will design and synthesise tools that exploit different transfer chemistries and labels, and express and purify Affimers that bind target proteins implicated in cancer. This toolset will be used to track proteins via live cell and super-resolution imaging, and to tag proteins and their interacting partners for isolation and analysis by proteomics. You will apply this platform to analyse proteins central to signalling networks that are dysregulated in cancer.

For this interdisciplinary project, you will join an ongoing collaboration of three groups with expertise in chemical biology/proteomics (Dr Wright), protein engineering (Dr Tomlinson) and super-resolution imaging (Prof. Peckham). This project would ideally suit a candidate with synthetic chemistry skills and a strong interest in applying chemistry to biological problems.

Omics component: This project will involve the use of quantitative, high resolution mass spectrometry-based proteomics to identify the proteins that are labelled by the tools in cells.

Contact person: Dr. Megan Wright (m.h.wright@leeds.ac.uk)

Deadline: Monday, January 07, 2019

findaphd link

Title: Structure and function of specialised ribosomes in the Drosophila melanogaster brain and testis

Project description: This project aims to understand how changes in ribosome composition alters ribosome structure and how this enables ribosomes to translate specific mRNA pools.?

Omics component: It will be using 2 omics approaches Ribo-Seq and TMT (quantitative mass spec).

Contact person: Julie Aspden (j.aspden@leeds.ac.uk)

Deadline: Monday, January 07, 2019

findaphd link

Title: Determining the role of molecular co-chaperones in virus infection: a novel antiviral approach

Project description: Viruses are associated with approximately 10-15% of human cancers, resulting in about 2 million new cases every year in the world. Research in the Whitehouse laboratory determines how viruses cause cancer and in collaboration with the Foster laboratory develops novel antiviral strategies to prevent infection and tumourigenesis. This project focusses on molecular chaperone pathways which are essential for protein homeostasis, particularly in cancers. For oncogenic viruses, molecular chaperones function as broad host factors required for viral protein folding and stability. Therefore viral proteins are exquisitely sensitive to perturbations in chaperone-related pathways, presenting a novel antiviral target. We have exciting data showing that the molecular co-chaperone, STIP1, is essential for the replication of the oncogenic virus, KSHV. This project will determine the role of molecular chaperones in KSHV biology and determine if inhibiting molecular co-chaperone function is a potential therapeutic approach for the treatment of this important human pathogen. This exciting multidisciplinary project will utilise cutting-edge methodology including quantitative proteomics, cell biology and medicinal chemistry.

Contact person: Adrian Whitehouse (A.Whitehouse@leeds.ac.uk)

Deadline: Monday, January 07, 2019

findaphd link

Title: MicroRNA evolution in placental mammals: Unravelling conservation and divergence in their regulatory mechanisms in early pregnancy in different placental mammals

Project description: This project brings together, in a novel manner, the research areas of placental and uterine biology, computational molecular evolutionary biology, as well as microRNA regulation to understand how miRNAs may have contributed to the emergence of placental mammals. The main focus of this project will be to undertake wet bench analysis to understand the role of phylogenetically restricted miRNAs and the genes they regulate.

Omics component: microRNA sequencing

Contact person: Niamh Forde (n.forde@leeds.ac.uk)

Deadline: Monday, January 07, 2019

findaphd link

Title: Mining large international genetic datasets to identify new therapeutic targets in giant cell arteritis through innovative genetic methodology

Contact person: Jenny Barrett (J.H.Barrett@leeds.ac.uk)

Link

Title: Gene expression network analysis to identify candidate drivers of treatment resistance in glioblastoma multiforme (GBM)

Project description: The aim of this project is to assess the transcriptional changes across GBM gene expression networks during therapy to highlight candidate molecules responsible for conferring (or facilitating transcriptional reprogramming to) a more treatment resistant state. This will be done using our existing, novel high-coverage RNAseq data (from pairs of primary and recurrent patient GBMs), supplemented with that being produced within a global consortium that we are part of.

Omics component: Transcriptomics data in the form of RNAseq, with the possibility to integrate genomic data (WES and WGS) from the same samples

Contact people: Alastair Droop (a.p.droop@leeds.ac.uk) or Lucy Stead (l.f.stead@leeds.ac.uk)

Deadline: Monday, January 21, 2019

findaphd link

Skip to toolbar