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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.

160 Search Results

350
Category:
Neuroscience
Project:

Memory formation during sleep

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

The laboratory investigates the interactions between episodic memory formation and brain dynamics during sleep. How are memories strengthened (‘consolidated’) overnight? What is the role of specific brain rhythms during sleep? Can we use sleep to experimentally control the extent of forgetting? To tackle these questions, a range of techniques including intracranial EEG, scalp EEG, MEG, fMRI, non-invasive brain stimulation (NIBS), and behavioural testing are used.

349
Category:
Immunology
Project:

CRISPR-mediated screens for Phosphoinositide signaling in T cell

Project Listed Date:
Institute or Center:
National Institute of Allergy and Infectious Diseases (NIAID)
University:
Cambridge
Project Details:

The Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that control diverse signalling pathways affecting gene-transcription, cellular adhesion and trafficking, autophagy and metabolism via the generation of PIP3. While some of these readouts are controlled by the evolutionarily conserved PI3K-AKT-FOXO, PI3K-AKT-mTOR axes, there is a diverse network of PI3K effectors that are less well studied, especially in lymphocytes, but which nonetheless can have profound effects on lymphocyte biology. We have recently used CRISPR/Cas9 to perform a targeted screen of PI3K effectors by generating a library that specifically targets PIP3-binding proteins. Screening for genes that affect T cell adhesion, we identified RASA3 as a key protein linking PI3K to the activation of the integrin LFA-1 and found that RASA3 is critical for T cell migration, homeostasis and responses to immunization. We have now generated extended CRISPR/Cas9 libraries that target the entire PI3K-ome (including the kinases, phosphatases and all known effector proteins). Potential projects include designing and implementing new screens for downstream readouts of PI function, including autophagy, endocytosis, regulation of humoral immunity in vivo or other readouts, and/or understanding how RASA3 regulates T cell function and the signaling pathways involving this key regulator of immune cell migration.

348
Category:
Computational Biology
Project:

Identifying germline and somatic genetic interactions that are relevant to patient outcomes in cancer

Project Listed Date:
Institute or Center:
National Cancer Institute (NCI)
UK Mentor:
N/A
University:
N/A
Project Details:

Since 2018, several studies have reported “germline-somatic interactions” across cancer types. However, such studies demonstrate extensive heterogeneity in defining the germline and somatic features involved or the specific mechanism of interaction (including predicted protein changes, cell lines/CRISPR screens, and immune system-associated phenotypes), and effectively none evaluate results clinically. We hypothesize that pan-cancer or breast-cancer-specific germline-somatic interactions will demonstrate associations with therapy in the metastatic setting. To test this, we will compile reported (a) germline-somatic variant interactions from papers and (b) datasets with individual-level treatment information and test the associations between these interactions and treatment response in metastatic breast cancer.

346
Category:
Neuroscience
Project:

The neural mechanism underlying multisensory learning during spatial navigation

Project Listed Date:
Institute or Center:
National Institute of Neurological Disorders and Stroke (NINDS)
NIH Mentor:

Dr. Yi Gu

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

Multisensory learning helps an individual learn through more than one sense. However, the underlying neural mechanism is unclear. In this study we aim to pursue this question in a spatial learning regime. We will focus on the medial entorhinal cortex (MEC), which plays a critical role in spatial learning and the dysfunction of which is closely related to Alzheimer’s disease. We will record neural dynamics of the MEC using two-photon imaging approach when mice navigate in virtual environments, in which multisensory spatial information will be precisely delivered. The goal of the project is to deeply understand how the neural response of the MEC contributes to multisensory learning.

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.

343
Category:
Computational Biology
Project:

Computational investigation of tumor microenvironment

Project Listed Date:
Institute or Center:
National Cancer Institute (NCI)
UK Mentor:
N/A
University:
N/A
Project Details:

We are interested in a variety of topics related to “Deciphering cellular heterogeneity in tumor microenvironment using single cell data”, “Functional characterization of tumor infiltrating T cells”, “Links between embryonic development and cancer”, “Functional characterization of non-coding somatic mutations”, and “Methods for single cell omics”. These projects involve non-trivial  methods development as well as sophisticated data analysis but the focus is always on the biological question. Our lab is involved in several collaborations with immunologists and cancer biologists.

341
Category:
RNA Biology
Project:

RNA regulation of lymphocyte activation and immunity 

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

Dr. Eugene Valkov

UK Mentor:

Prof. Martin Turner

University:
Cambridge
Project Details:

Lymphocytes respond to infection by rapidly increasing and decreasing the expression of many genes in a highly regulated manner. This regulation requires the integration of transcription, mRNA decay and translation. We are only just beginning to understand how these processes are integrated with each other.  The host labs are studying how the multiprotein CCR4-NOT complex and its associated RNA binding proteins control gene expression. By combining structural and molecular biology approaches with cellular immunology and mouse models of immune responses we offer a broad training experience and the opportunity to discover fundamental mechanisms of gene regulation in the immune system.
 

References:

The RNA m6A binding protein YTHDF2 promotes the B cell to plasma cell transition. Turner, D.J. Saveliev, A., Salerno, F., Matheson, L.S., Screen, M., Lawson, H., Wotherspoon, D., Kranc, K.R, & Turner, M. (2021). bioRxiv. 

Reconstitution of recombinant human CCR4-NOT reveals molecular insights into regulated deadenylation. Raisch, T., Chang, C.T., Levdansky, Y., Muthukumar, S., Raunser, S., Valkov, E. (2019). Nature Communications 10: 3173. 

RNA-binding proteins control gene expression and cell fate in the immune system.  Turner, M., and Díaz-Muñoz, M.D. (2018) Nature Immunology 19:120-129. 

340
Category:
Clinical Research
Project:

Therapeutic effects of microbiome manipulation in the treatment of eczema

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

Dr. Ian Myles

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

Our group focuses on how human health is affected by the normal microorganisms that live on our skin (collectively termed the microbiome). Our emphasis is on eczema (also called atopic dermatitis or AD), which is an inflammatory disease of the skin associated with reduced quality of life and high risk of developing asthma, allergic rhinitis, and food allergies. Recent work has uncovered that the skin microbiome is significantly different between healthy controls and patients with AD and that early commensal diversity may protect against development of AD. These realizations suggest that the skin microbiome contributes to AD presentation through both harmful and protective pathways. Our group identified a species of bacteria from normal healthy skin, called Roseomonas mucosa, which showed promising features in cell culture and mouse models that suggested the bacteria might be able to treat patients with eczema. We have since transitioned into a clinical trial using Roseomonas mucosa as a topical treatment for eczema. 

318
Category:
Developmental Biology
Project:

Understanding the self-organization of morphogenesis and collective cell migration in the zebrafish embryo

Project Listed Date:
Institute or Center:
National Institute of Child Health and Human Development (NICHD)
NIH Mentor:

Dr. Ajay Chitnis 

University:
Cambridge
Project Details:

The posterior Lateral Line primordium is a group of about a hundred cells that migrates under the skin, from the ear to the tip of the tail, periodically forming and depositing sensory organs called neuromasts, to spearhead formation of the zebrafish Lateral Line sensory system. In recent years, this relatively simple and accessible system has emerged as an attractive model for understanding various aspects of morphogenesis in the developing embryo, including the guidance of cell migration, tissue patterning and organ formation. The goal is to use a combination of cellular, molecular, genetic and biomechanical manipulations coupled with live imaging, image processing and the development of multi-scale computational models to understand the self-organization of cell-fate, morphogenesis and migration of the lateral line primordium. Specific focus will be on developing tools and methods for investigating, imaging, quantifying and modelling the mechanics of collective migration, morphogenesis of epithelial rosettes and the intercellular and intracellular signaling networks that coordinate lateral line primordium development.

247
Category:
Biomedical Engineering & Biophysics
Project:

Ultra-High Field (7T) Magnetic Resonance Imaging (MRI) Development

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

Prof. Chris Rodgers

University:
Cambridge
Project Details:

I founded a new ultra-high field (7T) MRI physics group in Cambridge in autumn 2017. We develop cutting-edge methods for studying the human brain and body using Cambridge’s state-of-the-art Siemens Terra 7T MRI scanner. My group have active collaborations with clinicians in clinical neurosciences, psychiatry, oncology, and cardiology (Papworth), and with experts in cognitive neuroscience. I welcome PhD students to join the group. The following are areas of strong interest from our community, which would be suitable to develop a PhD project in discussion with me.


(i) Developing new spectroscopic imaging pulse sequences to map neurochemical profiles across the whole brain in a single scan. We have hardware available to apply these methods to study metabolites containing 1H (e.g. NAA, creatine, GABA, GSH) or 31P (e.g. PCr, ATP, in vivo pH mapping) or 13C (e.g. labelled glucose or succinate).
(ii) Developing new methods for neuroimaging, particularly for imaging blood flow in small vessel disease, or for rapid, motion-corrected fMRI in deep brain nuclei.
(iii) Developing new metabolic imaging methods for use in the human body. These would use a new multinuclear (1H and 31P) whole-body coil being built for me by Tesla Dynamic Coils (Netherlands). This could be developed in collaboration with colleagues at Papworth and Radiology for studies in the heart.
(iv) Imaging of metabolism by 2H deuterium metabolic imaging (DMI). 

 

246
Category:
Cancer Biology
Project:

Using genome engineering approaches to understand the genes controlling tumour growth

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

Prof. Adrian Liston

University:
Cambridge
Project Details:

Tumour growth is intimately linked to the infiltration of leukocytes (immune cells). Recruitment of suppressive leukocytes can promote angiogenesis and tissue remodelling, while repulsion of pro-inflammatory leukocytes is required to prevent tumour rejection. To date, this process has been studied in a hypothesis-directed manner, identifying a role for gene X in leukocyte subset Y. Here we will use new genome engineering approaches to simultaneously test the impact of every known migration-associated molecule in every infiltrating leukocyte subset, in order to reach a truly comprehensive understanding of the genes controlling the entry of each cell type into the tumours.

 

This project is based around the cutting-edge “Pro-code” technology. “Pro-codes” allows up to 400 lentiviruses to be built, each with a unique protein-based barcode. 400 unique CrispR guideRNAs can be built into a barcoded lentivirus library, covering every known migration-associated gene (chemokine receptors, integrins, adhesion molecules, chemotactic receptors, matrix metalloproteases, etc). Transfection of inducible Cas9-expressing bone-marrow stem cells with the ProCode library creates a mouse where the immune system is a mosaic of 400 different knockout lines. Through ultra-high parameter single cell cytometry, we can compare leukocytes that stay in circulation, migrate to healthy tissue or enter tumour tissues. Relative enrichment and depletion of each barcode in each leukocyte subset provides a comprehensive genetic map of leukocyte entry into tumours.

245
Category:
Neuroscience
Project:

Neural bases of repetition priming

Project Listed Date:
Institute or Center:
National Institute of Mental Health (NIMH)
NIH Mentor:

Dr. Alex Martin

University:
Cambridge
Project Details:

Repetition priming (RP) is a basic form of memory, whereby prior exposure to a stimulus facilitates or biases subsequent responses to that stimulus. From a neuropsychological perspective, RP is interesting because it can occur without awareness, and despite the damage to the medial temporal lobe (MTL) system that produces amnesia. Many functional neuroimaging studies using fMRI and MEG/EEG have investigated the brain regions and neuronal dynamics associated with RP. However, the results are complex, depending on several important variables, and suggesting multiple underlying neural mechanisms. Recent computational models provide some insight, and the proposed project will extend these models to a broader range of neuroimaging data, including existing data from intracranial recording in human and non-human primates.

244
Category:
Neuroscience
Project:

Ultra-high field imaging of adaptive brain circuits

Project Listed Date:
Institute or Center:
National Institute of Mental Health (NIMH)
NIH Mentor:

Dr. Peter Bandettini

UK Mentor:

Prof. Zoe Kourtzi

University:
Cambridge
Project Details:

The human’s brain capacity for sensory plasticity has been studied mainly in the context of neurodevelopment (i.e. critical periods) and pathology (e.g. amblyopia) with interventional approaches (e.g. sensory deprivation) that result in drastic brain re-organisation. Yet, understanding the brain plasticity mechanisms that mediate subtler changes in perceptual judgments through shorter-term experience and training remains a challenge. 

This project focuses on the brains ability to improve perceptual skills at the core of visual recognition through training; that is, the ability to detect the features of an object from cluttered backgrounds and discriminate whether they belong to the same or different objects. Learning and experience have been suggested to facilitate this ability to translate complex patterns of visual information into perceptual decisions. We will exploit methodological advances in high-field (7T) brain imaging to investigate functional and neurochemical brain plasticity mechanisms at finer-scale. We will test the hypothesis that perceptual learning is implemented by feedback and inhibitory mechanisms that re-weight sensory information across stages of processing (from early to higher visual cortex). In particular, the high resolution of 7T imaging allows us to measure functional signals in different cortical layers. We will test whether learning alters fMRI activation patters in deep—rather than middle—layers in the visual cortex, consistent with feedback processing. Further, advances in MR Spectroscopy enable us to test the role of GABA—the primary inhibitory neurotransmitter for brain plasticity—in perceptual learning. We will test whether learning-dependent changes in GABA relate to changes in functional brain activity and improved behavioural performance in perceptual tasks. Investigating these core mechanisms of brain plasticity will advance our understanding of how the brain optimises its capacity to support adaptive behaviour through learning and experience.

243
Category:
Genetics & Genomics
Project:

Using population genomic approaches to evaluate Anopheles gambiae

Project Listed Date:
Institute or Center:
National Human Genome Research Institute (NHGRI)
NIH Mentor:

Dr. Adam Phillippy

University:
Cambridge
Project Details:

Population genomic approaches across diverse species have traditionally used short read sequence data to investigate population structure and signatures of selection. In the recent past, long reads are more traditionally used to build reference genomes to which the short read data can be aligned and evaluated. However, the cost of long read sequencing as well as the DNA input required to generate high quality long read data is dropping rapidly. We foresee a future where population genomics transitions to long read data.

 

Using these emerging technologies, this project will begin to evaluate what new insights are gained for the Anopheles gambiae species complex, a set of mosquito species famous as the vector of malaria and known to exhibit porous species boundaries and abundant structural variation.  We anticipate that long-read approaches for haplotype phasing and structural variant discovery will enable much clearer resolution of gene flow within species, introgression between species, and alleles under directional or balancing selection.  Insights gained from this project are likely to influence approaches taken for other species that are known to have similar complexities (e.g., Heliconius butterflies, African cichlid fishes).

 

This project will involve developing and applying new computational methods for analysing long-read sequencing data in an Anopheles population genomics context. The collaborating laboratories at the Sanger Institute and NHGRI are experts in these respective areas and well-suited to provide the appropriate mentorship.

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