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Research Opportunities

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Prospective Students

The goal of the NIH Oxford-Cambridge (OxCam) Scholars Program is to create, foster, and advance unique and collaborative research opportunities between NIH laboratories and laboratories at the University of Oxford or the University of Cambridge. Each OxCam Scholar develops a collaborative research project that will constitute his/her doctoral training. Each Scholar also select two mentors – one at the NIH and one in the UK – who work together to guide the Scholar throughout the research endeavor.

Students may select from two categories of projects: Self-designed or Prearranged. OxCam Scholars may create a self-designed project, which enables students to develop a collaborative project tailored to his/her specific scientific interests by selecting one NIH mentor and one UK mentor with expertise in the desired research area(s). Alternatively, students may select a prearranged project provided by NIH and/or UK Investigator(s) willing to mentor an OxCam Scholar in their lab.

Self-designed Projects: Students may create a novel (or de novo) project based on their unique research interests. Students have the freedom to contact any PI at NIH or at Oxford or Cambridge to build a collaboration from scratch. The NIH Intramural Research Program (IRP) represents a community of approximately 1,200 tenured and tenure-track investigators providing a wealth of opportunity to explore a wide variety of research interests. Students may visit https://irp.nih.gov to identify NIH PIs performing research in the area of interest. For additional tips on choosing a mentor, please visit our Training Plan.

Prearranged Projects: Investigators at NIH or at Oxford or Cambridge have voluntarily offered collaborative project ideas for NIH OxCam Scholars. These projects are provided below and categorized by research area, NIH Institute/Center, and University. In some cases, a full collaboration with two mentors is already in place. In other instances, only one PI is identified, which allows the student to select a second mentor to complete the collaboration. Please note that prearranged project offerings are continuously updated throughout the year and are subject to change.

17 Search Results

238
Category:
Microbiology and Infectious Disease
Project:

Transmission of bacteria and antimicrobial resistance determinants between and among animals and humans

Project Listed Date:
Institute or Center:
N/A
NIH Mentor:
N/A
University:
Cambridge
Project Details:

We are interested in the transmission of bacterial pathogens and AMR determinants at multiple scales from the within-hospital level to global networks. Projects are possible on many large-scale datasets, primarily using population genomic and phylogenetic approaches to investigate these processes.

227
Category:
Microbiology and Infectious Disease
Project:

Genetic contribution to host susceptibility in Nontuberculous mycobacteria infections

Project Listed Date:
Institute or Center:
National Institute of Allergy and Infectious Diseases (NIAID)
UK Mentor:

Prof. Andres Floto

University:
Cambridge
Project Details:

Nontuberculous mycobacteria (NTM) represent the most common mycobacterial infection in the developed world and are often difficult or impossible to treat. While exposure of humans to NTM is almost universal (most species are ubiquitous in the environment), pulmonary infection only occurs in certain individuals, suggesting a strong genetic contribution to host susceptibility.

 

Nontuberculous mycobacteria (NTM) represent the most common mycobacterial infection in the developed world and are often difficult or impossible to treat. While exposure of humans to NTM is almost universal (most species are ubiquitous in the environment), pulmonary infection only occurs in certain individuals, suggesting a strong genetic contribution to host susceptibility.


Our proposal aims to use both forward and reverse genetics to define and characterise host restriction factors for NTM infection. The project will employ the following orthogonal experimental approaches:


1) We will functionally test the impact of genetic polymorphisms, identified through the NIH whole exome sequencing study of NTM-infected individuals and family pedigrees ( Ref) using CRISPR-Cas9 genomic editing of macrophages and IPSC-derived epithelial cells.
 
2) In parallel, we will undertake an unbiased forward genetic screen using an established and validated genome-wide CRISPR-Cas9 macrophage library to phenotypically screen for mutants with defective restriction of intracellular NTM.

 
Validated hits from both approaches will be prioritised, based on novelty and effect size, for further analysis to examine (a) their molecular mechanism of action (using advanced cell imaging and biochemical techniques), (b) their effect on in vivo infection (using established fly, fish, and mouse models); and (c) the impact of potential therapeutic manipulation of implicated pathways  as host-directed therapy.

213
Category:
Microbiology and Infectious Disease
Project:

Mechanisms underlying DNA replication and cell cycle control in Plasmodium

Project Listed Date:
Institute or Center:
N/A
NIH Mentor:
N/A
University:
Cambridge
Project Details:

My group studies the human malaria parasite Plasmodium falciparum.  Collaborative PhD projects can be offered in research areas centered around Plasmodium DNA biology: we are particularly interested in the molecular mechanisms underlying DNA replication and cell cycle control in Plasmodium, which replicates by an unusual method called schizogony.  We are also interested in mechanisms for silencing and promoting the recombination of a family of key virulence genes called var genes - particularly the role that G-quadruplex DNA structures may play in var gene control.  In fact, we have recently discovered that G-quadruplexes and their helicases have more general roles in genome stability and evolution in the malaria parasite as well.

211
Category:
Microbiology and Infectious Disease
Project:

Understanding genetic susceptibility to nontuberculous mycobacterial infections

Project Listed Date:
Institute or Center:
National Institute of Allergy and Infectious Diseases (NIAID)
NIH Mentor:

Dr. Steve Holland

University:
Cambridge
Project Details:

TB remains the biggest infectious killer in the world despite >50 years of antimicrobial therapy. 10 million people get TB each year of whom nearly 2 million succumb to it. Yet this burden represents only 5-10% of those who get infected; 90% clear the infection on their own. Both the Ramakrishnan and the Holland labs are trying to solve the puzzle of why some individuals get TB disease. The two labs take different and complementary approaches to the problem. Holland runs an internationally known referral service that takes care of a unique cohort of patients with genetic susceptibility to nontuberculous mycobacterial infections. In the lab, they have mapped these susceptibilities to varied immune genes – IRF8 and GATA-2, myeloid growth factors, IL-12R, the GTPase Rac2, to name only a few. How and whether deficiencies in these genes causes susceptibility to TB remains a black box. Ramakrishnan’s approaches afford the opportunity to open this black box.

Her group has pioneered the optically transparent and genetically tractable zebrafish infected with Mycobacterium marinum as a model for TB. The use of the zebrafish has enabled discoveries about TB immunopathogenesis and the genetic basis of susceptibility to TB which has led to the discovery of a variety of inexpensive, approved drugs that can be used to treat TB, often in a patient genotype-directed manner.

Through this joint project, the two labs will work together to harness the power of the zebrafish to understand the molecular and cellular basis of the human susceptibilities identified by Holland. The student will move between humans and fish (and Bethesda and Cambridge) to uncover fundamental mechanisms of mycobacterial disease pathogenesis while acquiring mastery over the disciplines immunology, infectious diseases, genetics, molecular biology and cell biology.

210
Category:
Microbiology and Infectious Disease
Project:

Understanding natural immunity to malaria for better vaccine design

Project Listed Date:
Institute or Center:
National Institute of Allergy and Infectious Diseases (NIAID)
NIH Mentor:

Dr. Steve Holland

UK Mentor:

Prof. Julian Rayner

University:
Cambridge
Project Details:

There are more than 200 million clinical cases of malaria each year, leading to nearly half a million deaths, primarily among children in Africa. The two major tools for malaria control, antimalarial drugs and insecticides, are both seriously threatened by resistance, making the search for a highly effective malaria vaccine more urgent than ever. My lab focuses on the malaria parasite blood stages, during which parasites invade, multiply inside and consume human erythrocytes. The process of erythrocyte invasion represents a brief extracellular window in the parasite life cycle when parasites are exposed to the antibody-mediated immune system, making it a potential vaccine target. A number of vaccine-related projects are available that intersect with the interests of NIH collaborators in the NIAID Malaria Research Program, from systematic screening of new potential vaccine candidates, to deep structural understanding of current high-profile candidates, to understanding natural immunity to malaria in order to inform better vaccine design. All could involve a mix of new technologies, cutting edge experimental genetics, parasite biology and the opportunity to contribute to the long-term battle against one of humanities oldest and most persistent infectious disease foes.

207
Category:
Microbiology and Infectious Disease
Project:

Characterisation of parasite cell proteomes

Project Listed Date:
Institute or Center:
National Institute of Allergy and Infectious Diseases (NIAID)
NIH Mentor:

Dr. Michael Grigg

UK Mentor:

Prof. Ross Waller

University:
Cambridge
Project Details:

Apicomplexan pathogens are highly-adapted intracellular parasites of humans causing disease including malaria, toxoplasmosis and cryptosporidiosis. These parasites actively confront, subvert and defend themselves against host immune attack using a complex suite of parasite surface and secreted proteins that hijack immune signalling pathways. Moreover, transmission and generation of genetic novelty occurs in definitive hosts where differentiation into sexual parasite forms occurs. Relatively little is known, however, of the molecules and processes that drive these events, particularly during the sexual stages of parasite development. This project will use new methods in in vitro culture of sexual development in Toxoplasma, advanced methods for global spatial characterisation of parasite cell proteomes in order to identify specific proteins thought to be implicated in these interactions, and then utilise CRISPR/cas9 mutagenesis tools to engineer pools of strains deficient in these specific proteins. By assaying mutant pools both in vitro, and through the definitive host we will identify proteins and processes required for sexual stage conversion.

199
Category:
Microbiology and Infectious Disease
Project:

Structure and dynamics of bacterial chemotaxis signalling array by cryoEM

Project Listed Date:
Institute or Center:
N/A
NIH Mentor:
N/A
UK Mentor:

Prof. Peijun Zhang

University:
Oxford
Project Details:

Bacterial chemotaxis response is crucial for colonization and infection, and the signal transduction systems that mediate such responses are potential new targets for antimicrobial drug development. Such system has emerged as a paradigm for understanding the principles of intracellular signal transduction both in bacterial and eukaryotic cells. In bacterial cells, hundreds of basic core signalling units consisting of three essential components, the chemoreceptors, the histidine kinase and the adaptor protein, assemble into a two-dimensional lattice array which allows cells to amplify and integrate many varied and possibly conflicting signals to locate optimal growing conditions. We aim to determine the structure and dynamics of the chemotaxis signalling arrays using state-of-the-art cryo-electron microscopy and tomography. We will take both in vitro and in situ structural approaches and combined with large-scale all atom molecular dynamic simulations. The ultimate goal is to assemble a time-resolved molecular movie of the entire signalling pathway in bacterial chemotaxis at an atomic level. 

182
Category:
Microbiology and Infectious Disease
Project:

Host-parasite interactions in parasitic diseases, such as malaria

Project Listed Date:
Institute or Center:
N/A
NIH Mentor:
N/A
University:
Oxford
Project Details:

The Higgins laboratory are expert in the structural studies of host-parasite interactions in parasitic diseases such as malaria. They study how interactions at the heart of processes such as erythrocyte invasion are mediated. They explore how parasite surface proteins manipulate the human immune system. They examine antibodies produced in response to human vaccination and determine how these function, and they use this information to design improved vaccine components.

 

To discuss possible projects, contact: matthew.higgins@bioch.ox.ac.uk

180
Category:
Microbiology and Infectious Disease
Project:

Adjuvant- and vaccine- induced innate and adaptive immune activation in malaria

Project Listed Date:
Institute or Center:
N/A
NIH Mentor:
N/A
UK Mentor:

Prof. Anita Millcic

University:
Oxford
Project Details:

Development of vaccines against existing complex diseases (such as malaria), or emerging pathogens, requires innovative approaches and the use of immune stimulants known as adjuvants. During an immune response to a vaccine, orchestrated cellular activation and leukocyte migration promote rapid changes throughout the body, from the site of injection to secondary lymphoid organs, such as the tissue draining lymph nodes and the spleen, to peripheral blood and the liver.


This project will focus on the characterisation of the adjuvant- and vaccine- induced innate and adaptive immune activation across these sites, with the analysis of the vaccine localisation (using intravital imaging and/or multiparameter flow cytometry) and the resulting cellular phenotypes within the innate and adaptive compartments. 

Studies will be based on a mouse model of malaria, using the malaria vaccine developed at the Jenner Institute, R21 - a virus-like particle (VLP) analogous to the currently most advanced malaria vaccine, GSK’s RTS,S in AS01 adjuvant. The R21 vaccine will be combined with new clinically relevant liposome- and emulsion-based adjuvants. The profiles of the immune response to different formulations will be correlated with protection against malaria.

 

Training will be provided in animal work procedures: immunisation, tissue sampling, producing and isolating Plasmodium parasites for malaria challenge, as well as a variety of immuno-profiling techniques, such as ELISA, ELISpot, multiparameter flowcytometry, bead-based cytokine arrays, CyTOF, confocal and intravital microscopy and other relevant approaches.

163
Category:
Microbiology and Infectious Disease
Project:

Single cell proteomic and transcriptomic analysis of patients with monogenic forms of IBD

Project Listed Date:
Institute or Center:
N/A
NIH Mentor:
N/A
UK Mentor:

Prof. Holm Uhlig

University:
Oxford
Project Details:

Inflammatory bowel disease (IBD) encompasses two major diseases Crohn’s disease and ulcerative colitis. A subgroup of patients develop extreme phenotypes of intestinal inflammation due to rare monogenic defects. This includes several forms of immunodeficiency with diverse functional pathogenic mechanisms. Those defects inform on the importance of antimicrobial activity, hyperinflammatory responses and immune regulation. We investigate children with very early onset of intestinal inflammation using whole genome or whole exome sequencing to discover novel high impact genes and analyse the involved signaling pathways in vitro, in situ and in vivo. We like to understand the pathogenesis of rare “orphan” diseases to develop better treatment options for those disorders and improve understanding of pathogenic mechanisms of IBD as a whole.


The project will focus on single cell proteomic and transcriptomic analysis of patients with monogenic forms of IBD in order to understand functional mechanisms of monogenic IBD, to understand cellular communication and to identify novel therapeutic targets to induce cellular antimicrobial activity in order to maintain and reinstall intestinal mucosal barrier function.

159
Category:
Microbiology and Infectious Disease
Project:

Smartphone based image analysis for malaria diagnosis

Project Listed Date:
Institute or Center:
National Library of Medicine (NLM)
NIH Mentor:

Dr. Stefan Jaeger 

UK Mentor:

Prof. Richard Maude

University:
N/A
Project Details:

Malaria is a major burden on global health with about 200 million cases worldwide, and 600,000 deaths per year. Inadequate diagnostics is a major barrier to effective management of cases and elimination of the disease. The current gold standard method for malaria diagnosis is light microscopy of blood films. About 170 million blood films are examined every year for malaria, which involves manually identifying and counting parasites. However, microscopic diagnostics are not standardized and depend heavily on the experience and skill of the microscopist, many of whom work in isolation, with no rigorous system in place for maintenance of their skills. For false negative cases this leads to incorrect diagnosis with unnecessary use of antibiotics, a second consultation, lost days of work, and in some cases progression into severe malaria. For false positive cases, this results in unnecessary use of antimalarial drugs and side effects.

 

To improve malaria diagnostics, the Lister Hill National Center for Biomedical Communications, an R&D division of the U.S. National Library of Medicine, NIH and Mahidol-Oxford Tropical Medicine Research Unit, University of Oxford, in Bangkok, Thailand are developing a fully automated low-cost system that uses a mobile phone and standard light microscope for parasite detection and counting on blood films. Compared to manual counting, automatic parasite counting is more reliable and standardized, reduces the workload of the malaria field workers and reduces diagnostic costs. To count parasites automatically, the system uses image processing methods to find cells infected with parasites in digitized images of blood films. The system is trained on manually annotated images and machine learning methods then discriminate between infected and uninfected cells, detect the type of parasites that are present, and perform the counting. The system uses a regular smartphone and digital images acquired on standard light microscopy equipment making it ideal for resource-poor settings.

 

This PhD project will develop and test this system for real-world use for malaria diagnosis. It will include optimisation of the system at NIH and testing of the system in the field at MORU including the smartphone application interface and performance, the system for connecting the smartphone to standard light microscopes, development of a core set of performance metrics for the application, field testing of the entire system for malaria diagnosis together with government healthcare workers and National Malaria Control Programme staff, structured interviews to gather feedback on the system and its potential role in malaria diagnosis in different settings, a formal field trial of the system performance and development of a system implementation guidance document for National Malaria Control Programmes.

 

The student will join a dynamic team of image analysis specialists at NLM and epidemiologists, modellers and clinicians at the MORU offices in Bangkok. They will spend time at field sites in malaria-endemic areas and will interact with government staff. Training will be provided at NIH on basic image analysis and smartphone application development and at MORU on malaria miscroscopy, clinical study methodology, data analysis and research ethics.

126
Category:
Microbiology and Infectious Disease
Project:

Understanding the contribution of parasite genotype to Leishmaniasis outcomes

Project Listed Date:
Institute or Center:
National Institute of Allergy and Infectious Diseases (NIAID)
UK Mentor:

Prof. William James

University:
Oxford
Project Details:

Leishmaniasis is an important disease caused by protozoan parasites that are transmitted by infected sand fly bites in tropical and subtropical regions.  Depending on the strain of Leishmania, disease forms in humans range from localized, self-limiting cutaneous lesions to visceralizing infections that are fatal in the absence of treatment.   The specific contribution of parasite genotype to disease outcome remains largely unknown. Taking advantage of a recently revealed sexual cycle that occurs during Leishmania development in the insect vector, our goal is to generate a series of hybrids between cutaneous and visceral strains that will be phenotyped in mouse models of cutaneous and visceral leishmaniasis.  Each hybrid will be subjected to whole genome DNA and RNA-sequencing to follow parental allele, structural variation, including chromosome somy, gene expression, and epigenetic differences that associate with disease outcome.  Experimental approaches will involve genetic manipulation of the parasite, DNA and RNAseq analysis, single cell genomics, and the application of various computational/bioinformatics methods developed to facilitate QTL and GWAS studies that identify linkage between genes and phenotypes. 

119
Category:
Microbiology and Infectious Disease
Project:

Host response in Lyme disease: investigating factors associated with local control, dissemination and persistence.

Project Listed Date:
Institute or Center:
National Institute of Allergy and Infectious Diseases (NIAID)
UK Mentor:
N/A
University:
N/A
Project Details:
N/A
117
Category:
Microbiology and Infectious Disease
Project:

Cellular and Molecular Biology of Malaria Parasites

Project Listed Date:
Institute or Center:
National Institute of Allergy and Infectious Diseases (NIAID)
NIH Mentor:

Dr. Sanjay Desai

UK Mentor:
N/A
University:
Oxford
Project Details:

Malaria remains an important global health problem; with increasing drug resistance and the lack of an effective vaccine, new therapies are needed and should be based on a rigorous understanding of parasite biology. Our NIAID lab has used a multidisciplinary approach to discover and characterize the three known ion channels in bloodstream malaria parasites. Through academic and pharmaceutical collaborations, we have also found potent inhibitors that are being pursued as new antimalarial drugs. Research projects will be tailored to the interests of the trainee and expertise available in possible collaborator labs. These projects may utilize molecular biology including CRISPR and heterologous expression, structural biology including cryoEM, biochemical methods including electrophysiology, epigenetics, and high-throughput screening for drug discovery.  These and other methods are actively used in the lab. Dr. Desai has collaborators at Oxford, Cambridge, and Wellcome Sanger, depending on project.

115
Category:
Microbiology and Infectious Disease
Project:

Rational strategies for TB vaccine development

Project Listed Date:
Institute or Center:
National Institute of Allergy and Infectious Diseases (NIAID)
NIH Mentor:

Dr. Clif Barry

UK Mentor:

Prof. Helen McShane

University:
N/A
Project Details:

There is an urgent need for an improved TB vaccine. Advances in CRISPR/CAS technology in Mycobacterium tuberculosis have created the opportunity to rapidly evaluate novel knock-outs/knockdowns in this organism. With an improved understanding of the outer cell envelope of this deadly pathogen we aim to systematically construct and evaluate mutants in critical, highly exposed proteins present on the surface of Mtb cells to identify potential candidate vaccines that would be evaluated in cellular and animal models. This project has an overall goal of advancing both our understanding of the host immune response and the role of bacterial surface proteins in mycobacterial survival in vivo.

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