header-bg

Research Opportunities

Background Header
Image
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

345
Category:
Virology
Project:

HIV-1 Env incorporation and maturation

Project Listed Date:
Institute or Center:
National Cancer Institute (NCI)
NIH Mentor:

Dr. Eric Freed

UK Mentor:

Prof. Peijun Zhang

University:
Oxford
Project Details:

The formation of infectious HIV-1 particles requires the incorporation of Env glycoproteins during the assembly process, with Env mediating binding of newly released virions to target cells and subsequent entry via fusion between viral and target-cell membranes. The interaction between the MA domain of Gag and gp41 of Env plays a central role in Env incorporation into virions and in the activation of Env fusion activity, yet this interaction remains poorly understood at the biochemical and structural levels. In addition, recent structures of the MA lattice in both immature and mature HIV-1 particles implicate a maturation-induced rearrangement of MA the lattice. This opens the possibility that MA-gp41 interactions are dynamic, and change during the maturation process.

We aim to apply an array of biochemical, structural, super-resolution imaging, and virological approaches that will interrogate the MA/gp41 interaction and will provide novel insights into the mechanism and dynamics of Env incorporation into HIV-1 particles. A set of informative mutants, which display stabilized MA-MA and/or MA-gp41 interactions, will be used for structural studies,. Cryo-ET analysis of intact mature and immature virions will be performed to obtain structural data that will complement the information obtained with the MA/Gag assemblies. Predictions regarding potential sites of MA-MA and MA-gp41 interactions obtained from these structural studies will be tested in Env incorporation and virus replication assays. This combination of structural, biochemical, and virological studies will help to elucidate the mechanism of Env incorporation into HIV-1 particles and the subsequent process of particle maturation.

344
Category:
Virology
Project:

Imaging HIV-1 nuclear import by in situ cryo-tomography and correlative microscopy

Project Listed Date:
Institute or Center:
National Cancer Institute (NCI)
NIH Mentor:

Dr. Vinay Pathak

UK Mentor:

Prof. Peijun Zhang

University:
Oxford
Project Details:

Human immunodeficiency virus type 1 (HIV-1) is the causative agent behind acquired immunodeficiency syndrome (AIDS) that currently has no cure or vaccine. While antiviral treatments are effective, the rise of drug-resistant strains has become a growing concern. HIV-1 primarily infects the immune system, targeting CD4+ T cells and macrophages and is a lentivirus known to be able to infect non-dividing cells, requiring it to exploit nuclear import mechanisms. This process is dependent on the viral capsid. The HIV capsid is a conical structure that houses the genomic material of the virus. It needs to be metastable in order to be protective while allowing timely disassembly (termed uncoating) to release its genome. The dynamics of the capsid nuclear import and uncoating are still unknown and are modulated by host dependency and restriction factors.

We aim to apply multi-imaging modalities to investigate uncoating and nuclear import of HIV. These will include super-resolution fluorescence microscopy (including the newest MINFLUX technology), Focused Ion Beam and Scanning electron microscopy (cryoFIB/SEM), cryo-electron microscopy and cryo-electron tomography (cryoEM/ET). The viral core and host factors will be fluorescently tagged, and infection will be monitored from viral attachment to nuclear import. The sample will be cryo-preserved and imaged by cryoEM/ET and cryoFIB/SEM. The combination of these imaging techniques, paired with molecular biology and virology tools, will yield unparalleled knowledge of the HIV infection process within the native cells, providing the framework for development of novel therapeutics targeting HIV infection in the future.

212
Category:
Virology
Project:

Viral interferon responses

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

Prof. Yorgo Modis

University:
Cambridge
Project Details:

All viruses deliver or generate RNA in the cytosol. Long cytosolic dsRNAs are recognized by the innate immune sensor MDA5. My group has shown that MDA5 assembles into filaments on dsRNA, which activates the signaling hub protein MAVS and induces a potent antiviral interferon response.

198
Category:
Virology
Project:

Structural mechanisms of HIV-1 inhibition by host cell factors using cryoEM

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

Prof. Peijun Zhang

University:
Oxford
Project Details:

Infections by retroviruses, such as HIV-1, critically depend on the viral capsid. Many host cell defence proteins, including restriction factors Trim5α, TrimCyp and MxB, target the viral capsid at the early stages of infection and potently inhibit virus replication. These restriction factors appear to function through a remarkable capsid pattern sensing ability that specifically recognizes the assembled capsid, but not the individual capsid protein. Using cutting-edage cryoEM technologies, we aim to determine the molecular interactions between the viral capsid and host restriction factors that underpin their capsid pattern-sensing capability and ability to inhibit HIV-1 replication. Specifically, we will combine cryoEM and cryoET with all-atom molecular dynamics simulations to obtain high-resolution structures, together with mutational and functional analysis, as well as correlative light and cryoEM imaging of viral infection process, to reveal the essential mechanism for HIV-1 capsid recognition and inhibition of HIV-1 infection. Information derived from our studies will allow to design more robust therapeutic agents to block HIV-1 replication.

193
Category:
Virology
Project:

Simultaneous host and pathogen ’omics to interrogate the HIV reservoir

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

Prof. John Frater

University:
Oxford
Project Details:

The aim of this project will be to apply Next Generation Sequencing (NGS) approaches simultaneously to both host and the HIV provirus. The candidate will apply and improve methods to produce full-length viral haplotype and integration site data (already developed in the lab) from cohorts of individuals with treated early HIV infection, many of whom will receive experimental interventions and stop antiretroviral therapy.

 

Simultaneously, unbiased transcriptomic profiling (RNASeq) and analysis of DNA accessibility (ATAC-Seq) will be incorporated to allow a global interrogation of viral and host genomics, with potential to extend this to single cell analyses. Following method development, clinical samples from UK cohorts will be analysed to characterise the reservoir and to inform the source of rebound viraemia on treatment interruption. The work will therefore have both a cross-sectional and longitudinal component, promising significant analytical power. Working collaboratively with other group members and projects to link cell phenotype and subset with viral phylogenetics to identify the source of viraemia will be an important part of the work.

 

The candidate would be expected to have interests in both the laboratory wet-lab and bioinformatic components of the project, to achieve a unified problem-solving approach.

191
Category:
Virology
Project:

Examining the HIV reservoir 

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

Prof. John Frater

University:
Oxford
Project Details:

1. Biomarkers of the HIV reservoir and remission in primary HIV infection
2. Simultaneous host and pathogen 'omics to interrogate the HIV reservoir
3. Microfluidic and Lab-on-a-Chip approaches to characterising the HIV reservoir

190
Category:
Virology
Project:

Study cell and molecular biology of influenza A virus replication

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

Dr. Jonathan Yewdell

UK Mentor:

Prof. Ervin Fodor

University:
Oxford
Project Details:
N/A
184
Category:
Virology
Project:

Understanding mechanisms of sex disparities in infectious diseases

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

The mortality rate for COVID-19 pandemic has been two-fold higher in men than women. Similar observation extends to susceptibility and outcome of most other infectious diseases. For instance, after initial Hepatitis C Virus infection women are 2-3 times more likely to spontaneously clear the virus without any interventions and in HIV infection females are 5 times more likely to achieve elite control (complete suppression virus without therapy) than men. However, a consequence of the more vigorous immune response observed in females is more immunopathology and auto-immune diseases (such as lupus) in women than men. For the same reasons, females make stronger immune responses to vaccines but suffer more adverse events. Despite large evidence for sex differences in autoimmune diseases and susceptibility and outcome of infectious diseases, data addressing the biological mechanism are remarkably scarce.

 

In this project you will use computational and experimental methods to probe differences in immune system that lead to sex differences in infectious diseases. We will investigate this question across many infections including HCV, HBV, HIV and COVID-19. You will start with analysing the available RNA-seq and genomic data from our cohorts and other public databases to understand the role of heterogeneity in X chromosome inactivation in female immune cells and the transcriptional consequence and its contribution to better outcome in infectious diseases. In the next stage you will stimulate male and female immune cells with different immunogens and perform single cell RNA-sequencing to evaluate differential responses across distinct cell types and their association with sex. The project will also use samples and data from vaccine clinical trials. The baseline samples will be compared to the post-vaccination samples and differences in immune systems between sexes will be investigated.

172
Category:
Virology
Project:

Investigating the mechanisms of assembly, secretion and immune subversion adopted by (+)RNA viruses, such as Dengue/Zika and SARS-CoV-2

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

Prof. Sumana Sanyal

University:
Oxford
Project Details:

This project will investigate mechanisms of assembly, secretion and immune subversion adopted by (+)RNA viruses, with a particular emphasis on Dengue/Zika from the flavivirus and SARS-CoV-2 from the coronavirus families. Current understanding on how small (+)RNA viruses assemble and spread from cell to cell while evading innate and cellular immune responses is limited. Virus-infected cells induce selective autophagy of lipid droplets, which is accompanied by massive reorganisation of the host secretory pathway, but downregulate MHC-I and II restricted antigen presentation and often interferon production.

We have identified host factors that are targeted by viral proteins to induce autophagy-mediated LD hydrolysis (lipophagy) and unconventional secretory processes1,2. Collectively they are crucial for formation of viral replication compartments, assembly and cell-to-cell spread of virus progenies. We will apply CRISPR/Cas9 gene editing technology combined with biochemical and cell biological methods and functional assays to investigate how specific genes affect virus assembly and secretion. 

Infection by Dengue/Zika and SARS-CoV-2 also results in dramatic reduction of MHC-I and II restricted antigen presentation in monocytes and monocyte-derived cells. We will address how these viruses subvert innate and cellular immune responses to drive pathogenesis3,4. We aim to delineate biosynthesis, assembly, transport and turnover of MHC-molecules to define the specific steps targeted by these viruses. We will test E3 ligase candidates that are induced and copurify with MHC-I and II from virus infected cells, that may degrade or mis-sort MHC molecules to evade host immunity. We will combine quantitative mass spectrometry with complementary approaches in biochemistry, cell biology, immunology and virology to investigate the interplay of host cellular pathways such as autophagy, with that of virus biogenesis, and their mode of host immune evasion.

143
Category:
Virology
Project:

Regulation of Hepatitis B Virus Infection by Hypoxic Signaling Pathways.

Project Listed Date:
Institute or Center:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NIH Mentor:

Prof. Jake Liang

University:
Oxford
Project Details:

Viruses are obligate parasites that have evolved to manipulate their host to their advantage. Chronic viral infection of the liver is a global health problem, with over 300 million individuals infected with hepatitis B (HBV) or C (HCV) virus that causes liver disease which can progress to liver cancer. Viral hepatitis-related liver disease is the number 4 disease-related killer worldwide and is associated with more than 1 million deaths/year, highlighting an urgent need for new curative treatments. We recently discovered that low oxygen environments, naturally found in the liver, enhance HBV replication at several steps in the viral life cycle. Similar condition may apply to HCV replication. Cellular response to low oxygen is regulated by a family of oxygenases and hypoxia inducible factors (HIFs) that control genes involved in energy metabolism and other cellular processes. This project will study the role of hypoxic signaling and related metabolic pathways in HBV or HCV replication and their impact on pathogenesis, immune based and epigenetic therapies.

 

The successful candidate will investigate the molecular mechanisms underlying these observations. In particular, we will (i) identify the role of HIFs in HBV cccDNA biogenesis, transcription and metabolism, and production of infectious particles, and conduct comparative studies in HCV replication (ii) analyze how these host-virus interactions are shaped by the tissue microenvironment, genetic manipulations and metabolic parameters. The project has basic and translational research components and applies state-of-the-art technologies, tools and model systems to study HBV infection and its mechanism of disease. Taken together, this exciting project builds on strong preliminary results and existing expertise that may lead to new therapeutic targets and antiviral development.

130
Category:
Virology
Project:

Viral disease pathogenesis and vaccine development

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

Dr. Vincent Munster

University:
Oxford
Project Details:

Some of the most globally impactful diseases are caused by emerging and re-emerging viral pathogens. We have a long-standing collaboration with Vincent Munster at the NIH, investigating disease pathogenesis and developing vaccines against a number of outbreak pathogens.
 
This project represents an opportunity to join this world-class team to advance these works, investigating the mechanisms of disease, deriving correlates of protection, testing new therapeutic interventions and deriving structural determinants of disease through collaboration with Prof. Thomas Bowden.

128
Category:
Virology
Project:

Understanding the “immunodominance” of Ab responses to Influenza A glycoproteins, HA and NA 

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

Dr. Jonathan Yewdell

University:
Oxford
Project Details:

Influenza A virus imposes a significant socio-economic burden on humanity.  Vaccination is effective in only 60% of individuals, even under optimal circumstances.  The difficulty stems from the remarkable ability of influenza A virus to evade existing immunity.  IAV’s error prone polymerase enables the rapid antigenic evolution of the two virion surface glycoproteins, neuraminidase (NA) and hemagglutinin (HA).  Since the most potent antibodies (Abs) at neutralizing viral infectivity are directed the HA and NA globular domains, amino acid substitutions in these regions enable IAV to evade Ab-based immunity.  The project focuses on understanding the “immunodominance” of Ab responses to HA and NA in humans.  Immunodominance describes the strong tendency of the immune response to respond to complex antigens in a hierarchical manner, with higher ranking, “immunodominant” antigens potentially suppressing (“immunodominating”) responses to “subdominant” antigens.  By focusing responses on single antigenic sites, it is likely responsible for enabling influenza A virus to evade immunity by allowing the virus to sequentially alter its antigenicity.

127
Category:
Virology
Project:

Study cell and molecular biology of influenza A virus replication.

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

Dr. Jonathan Yewdell

UK Mentor:

Prof. Ervin Fodor

University:
Oxford
Project Details:
N/A
124
Category:
Virology
Project:

Understanding HIV incidence and impact of interventions  

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

Dr. Thomas Quinn

University:
Oxford
Project Details:

Understanding HIV incidence at a population level is critical for monitoring the epidemic and understanding the impact of interventions. Using full length sequencing of HIV we are developing models for estimating incidence based on viral diversity which increases with time in the infected host. Using data from longitudinal cohorts we will develop these models and then apply them to large population based interventions to determine their impact.  Experimental approaches include next-generation sequencing, phylogenetic analysis, modelling and statistical methodologies.

121
Category:
Virology
Project:

What makes bats good reservoirs of zoonotic viruses?

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

Dr. Vincent Munster

University:
Cambridge
Project Details:

A growing number of emerging infectious diseases, often with high fatality rates, have been traced back to bats, one of the most diverse and still mysterious order of mammals. Together with Dr Munster, my group is part of an international consortium investigating the association between Henipaviruses and their bat hosts on three continents (https://www.bat1health.org/). This project will combine laboratory work in the NIH Laboratory of Virology with mathematical modelling and bioinformatics at the University of Cambridge. The goal will be to model the interactions between viruses and the immune system of bats, in order to understand the role of within-host dynamics in the maintenance and shedding of zoonotic viruses in bat populations. There may be opportunities to take part in field work in Africa too. Specific research and learning objectives will be tailored to the student’s profile and interests.

Back to Top