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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.

53 Search Results

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650
Category:
Neuroscience
Project:

Mechanisms of perception and cognition 

Project Listed Date:
Institute or Center:
National Eye Institute (NEI)
NIH Mentor:

Dr. Bevil Conway

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

Mechanisms of perception and cognition 
Section on Perception, Cognition, and Action, Laboratory of Sensorimotor Research (NEI/NIMH)

Students would have the option to work on any project in the lab, and to take it in new directions. Current projects in the lab aim to understand the normal brain processes by which physical signals that impinge on the sensory apparatus (eyes, ears) are transformed into perceptions, thoughts, and actions. Work in the lab has been especially invested in developing color as a model system. The advantage of color is that its physical basis (wavelength) is well characterized, yet these chromatic signals support not only low-level visual abilities such as color matching but also high-level cognitive processes such as categorization, memory, social cognition, and emotion. This variety of phenomena provides a rich opportunity for investigating the full scope of perceptual and cognitive computations that make human vision such an important source of information about the world. The lab uses many research techniques, including psychophysics and non-invasive brain imaging (MRI, MEG) in humans, along with fMRI-guided microelectrode recording, fMRI-guided pharmacological blockade, microstimulation, tract-tracing, and computational modeling in non-human primates (NHPs). Work in the lab is organized around Four broad approaches:

First, the use of MRI in humans and NHPs to investigate homologies of brain anatomy and function between these species, to support the applicability of neurophysiology from NHPs to the human case, and to test hypotheses about the fundamental organizational plan of the cerebral cortex in the primate.

Second, the use of well-controlled psychophysics (including longitudinal experiments) combined with microelectrode recording in NHPs to show on a mechanistic level how populations of neurons drive behaviors such as perceptual decisions, categorization, and concept formation and memory.

Third, comparative psychophysical studies in humans and NHPs, as part of a program of neuroethology to understand the relative computational goals of perception/cognition in different primate species. In addition to studies of vision, the lab conducts experiments using auditory and combined audio-visual stimuli, to understand common principles of sensory-cognitive information processing, and to determine how signals across the senses are integrated into a coherent experience.

Fourth, large-scale neurophysiological experiments combined with cutting-edge analysis methods including machine learning, to determine the mechanisms of high-acuity visual perception at the center of gaze. We have developed several eye-trackers that afford photo-receptor resolution, providing an unprecedented look at fine-scale spatial and chromatic processing of the foveal representation in primary visual cortex. 
 

649
Category:
Neuroscience
Project:

Investigating brain tumor signaling and development of therapeutics

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

Dr. Zhengping Zhuang

UK Mentor:

Dr. Harry Bulstrode and 
Dr. Justin Lathia (Cleveland Clinic)

University:
Cambridge
Project Details:

This collaboration will provide the opportunity to work on malignant brain tumors in the laboratories of these three investigators with complementary expertise. The Zhuang laboratory (NIH) has an interest in the investigation of hypoxia (HIF-2a) signaling and tumor development as well as the pathogenesis of brain tumors and development of therapeutics. The Bulstrode laboratory (Cambridge) has an interest in neural stem cell identity and microenvironment interactions in brain development and in brain tumors. The Lathia laboratory (Cleveland Clinic) has an interest in cancer stem cells, tumor microenvironment interactions, immune suppression, and sex differences in brain tumors. The prospective student will have access to mentorship, infrastructure, and resources across all three laboratories. 

643
Category:
Neuroscience
Project:

Mechanisms of flexible cognition in neurological diseases

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

Patients with neurological diseases often have difficulty in evaluating, planning and initiating actions. This can lead to disorders of motivation, such as apathy and impulsivity. My group studies the cognitive neuroscience of goal-directed action, in the context of disease. Some patients have difficulty evaluating a particular plan in a given context. For example, they might revert to habitual actions which were previously associated with reward, or may be unable to think beyond their current situation. We take a multimodal approach, with behavioural studies, eye tracking, drug studies in healthy people and patients, EEG and neuroimaging. I have also developed computational models – both in the form of abstract cognitive models, and neural network simulations, to understand what the brain computes when determining actions.

My group has found that dopamine plays an important role in energising goal-appropriate actions. We hypothesise that prefrontal goal representations act through corticostriatal loops, being amplified or attenuated by dopamine.  In this project, the student will study patients with Parkinson’s disease and the effects of dopaminergic drugs on cognition, together with neuroimaging (which can include MEG or fMRI), to understand goal-directed action selection and energisation. The student will design their own behavioural tasks to separate out the component processes involved in maintaining and using goal information to energise actions. The student will test patients on their task, test drug mechanisms using a within-subject neuroimaging design, and  deploy appropriate analysis methods with help from a postdoctoral researcher.   The project will also include the opportunity to learn computational modelling if the student is keen.

638
Category:
Neuroscience
Project:

Building a Sexually Dimorphic Nervous System

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

Sex differences often represent the most dramatic intraspecific variations seen in nature. Although males and females share the same genome and have similar nervous systems, they differ profoundly in reproductive investments and require distinct morphological, physiological, and behavioural adaptations. Animals determine sex early in development, which initiates many irreversible differentiation events that influence how the genome and environment interact to produce sex-specific behaviours. Across taxa, these events converge to regulate sexually dimorphic gene expression, which specifies sex-typical development and neural circuit function. However, the molecular programs that act during development remain largely unknown. 

We aim to understand the gene regulatory networks underlying sexually dimorphic neuronal development in the brain of the genetically tractable vinegar fly Drosophila melanogaster. We are using single-cell technologies to compare the molecular profiles of both males and females in the developing central brain to understand the mechanisms underlying sexual dimorphism in the nervous system. The fly's central brain is a remarkably complex tissue composed of approximately 100,000 interconnected neurons, forming the intricate networks necessary to coordinate complex cognitive and motor functions. Tightly regulated molecular programs act over a broad developmental window leading to the diversity of cell types found in the brain. The proposed experiments will paint a detailed picture of cellular and molecular diversity in a developing central nervous system. Our data will answer the longstanding question: How are neuron types associated with sexual behaviours born and wired?

Lab website: 
http://www.oxfordcircuits.com/

Contact: Stephen F. Goodwin stephen.goodwin@cncb.ox.ac.uk 

636
Category:
Neuroscience
Project:

Investigating cytotoxic neuroimmune interactions in painful nerve injury

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

The sensory nervous system is a target for recognition by various immune factors after painful nerve injury (Davies et al., 2020; PMID: 32153361). While we know a great deal about immune mechanisms causing pain, we are only just beginning to understand the role it plays in its resolution. We have previously shown that nerve injury upregulates the stress ligand RAET1 that signals to natural killer (NK) cells via the immune receptor NKG2D. This neuro-immune interaction results in the pruning of intact primary sensory axons within the injured nerve (Davies et al., 2019; PMID: 30712871), that are otherwise a significant risk factor in neuropathic hypersensitivity (Kim et al., 2023a; PMID: 37366595). This neuro-immune interaction raises the possibility of an immune-based therapy for the treatment of neuropathic pain (Kim et al., 2023b; PMID: 37385878).

We use a combination of cell culture and mouse models to interrogate the receptor-ligand interactions between the peripheral nerve and killer immune cells injury and disease. We work closely with clinicians to collect and analyse relevant human samples and perform translational mechanistic studies using humanised cell culture models. Students will have the opportunity to learn animal behaviour, stem cell technology, live-imaging and high-dimensional flow cytometry, among other techniques, to understand the cellular and molecular interactions involved in cytotoxic neuro-immunity and its consequences for neuronal function and pain.

635
Category:
Neuroscience
Project:

AI-driven brain-wide credit assignment

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

We are at an exciting turning point in neuroscience. New technologies now allow us to measure and control neural activity and behaviour with unprecedented detail (Landhuis et al. Nature 2017, Lauer et al. Nature Methods 2022). At the same time, new theoretical frameworks are starting to reveal how rich behaviours arise from synaptic, circuit, and systems computations (Richards et al. Nature Neuroscience 2019). We are contributing directly to the latter by aiming to understand how we learn. To this end, we are developing a new generation of computational models of brain function guided by deep learning principles. We focus on understanding how a given behavioural outcome ultimately leads to credit being assigned to trillions of synapses across multiple brain areas – the credit assignment problem. To survive and adapt to dynamic and complex environments animals and humans must assign credit efficiently. Recently, we have shown that the brain can approximate deep learning algorithms (Sacramento et al. NeurIPS 2018, Blake et al. Nature Neuroscience 2019, Greedy et al. NeurIPS 2022, Boven et al. Nature Comms 2023). In this project, you will build on our state-of-the-art computational models of AI-like credit assignment in the brain and contrast it with recent experimental observations at the behavioural, systems, and circuit levels.

633
Category:
Neuroscience
Project:

Elucidating disease mechanisms in cerebellar ataxia using stem cell technology

Project Listed Date:
Institute or Center:
National Heart, Lung, and Blood Institute (NHLBI)
NIH Mentor:

Dr. John A. Hammer

University:
Oxford
Project Details:

The spinocerebellar ataxias (SCAs) are a complex group of neurodegenerative diseases that affect the cerebellum and result in the loss of motor coordination. No effective treatments exist for the SCAs, and there is a pressing need for better models in which to study the underlying disease-causing mechanisms and to identify potential therapies.

The aim of this project will be to develop novel stem cell-derived models to identify common pathological mechanisms in SCA that could be targeted therapeutically. The Becker group has identified several novel SCA mutations that highlight mGluR1-TRPC3-IP3R1 signaling as a key pathway affected in disease. Both research groups have developed complementary stem cell-derived and primary cerebellar models that provide unique systems to investigate the functional consequences of disease gene mutations in cerebellar Purkinje cells, which are the neurons that are primarily affected in SCA. 

The project will employ human induced pluripotent stem cells (iPSCs) that will be differentiated into cerebellar neurons and three-dimensional organoids and deeply phenotyped using a combination of functional experiments including calcium imaging, super-resolution imaging, and morphological analyses. In addition, functional analyses will be carried out in primary Purkinje cells. Identified disease phenotypes will subsequently be screened for potential therapeutics.

Becker Group website: 
https://www.ndcn.ox.ac.uk/research/cerebellar-disease-group

Hammer Group website: 
https://irp.nih.gov/pi/john-hammer 

631
Category:
Neuroscience
Project:

How emotional and semantic similarity influences episodic memory for emotional events

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

Dr. Deborah Talmi

University:
Cambridge
Project Details:

The student will explore a fundamental question in cognitive neuroscience, inspired by state of the art computational models of episodic memory. Their project will include collection of new empirical data, modelling the data computationally, and then testing a joint neural-cognitive model of memory recall using fMRI, where analysis will use RSA techniques.

630
Category:
Neuroscience
Project:

Using long read sequencing to explore the genomic causes of the major neurodegenerative diseases

Project Listed Date:
Institute or Center:
National Institute on Aging (NIA)
UK Mentor:

Dr. Mina Ryten

University:
Cambridge
Project Details:

Over the last 10 years, genome wide association studies (GWAS), exome and short-read genomic sequencing have enabled a revolution in our understanding of the genetic basis of neurodegenerative diseases, their progression and disease pathways. Despite this progress, our molecular understanding of the genes and loci that cause neurodegeneration remain limited, evidenced by the near absence of disease-modifying treatments for these diseases. In part this is because we have lacked the technology to fully characterise these important genomic regions. Short reads cannot fully assemble complex genomic rearrangements especially repetitive sequences, nor can they accurately and unambiguously identify or quantify different expressed isoforms. Therefore, the hypothesis underlying this PhD project is that significant inaccuracies in our knowledge of the genomic structure and transcript annotations at neurodegenerative disease loci have limited our understanding of disease pathogenesis.

To address this knowledge gap, the student will generate and analyse high quality paired long-read DNA and RNA-sequencing data to accurately investigate and annotate loci of interest in human brain samples, and in purified cell populations, across a range of neurodegenerative diseases. The student will use this new genomic and transcriptomic map to re-assess both GWAS risk SNPs at these loci and the pathogenicity of rare variants identified through WGS of patients with hereditary forms of neurodegeneration, so leveraging data generated within this project and that already available publicly. Thus, the student will help generate a core resource of annotated pathogenic loci to drive the identification of novel disease mechanisms, genetic causes and therapeutic targets in neurodegeneration.

625
Category:
Neuroscience
Project:

Regulation of synapse development, growth and plasticity

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

Dr. Mihaela Serpe

University:
Cambridge
Project Details:

Synaptic plasticity is fundamental to nervous system development and function.  Our labs have been studying BMP and reactive oxygen species (ROS) signalling as key regulators of synapse development, growth and plasticity. For example, during critical periods of nervous system development, metabolic ROS generated in mitochondria specify the functional ‘baseline’, including through setting the size and composition of synaptic terminals. The mechanisms by which this is achieved can now be explored. Specifically, we are now investigating:
 -    novel facets of BMP signalling, and their roles in regulating synapse size, composition and transmission properties;
 -    how transient critical period experiences in the late embryo lead to dramatic, lasting changes in gene expression and neuronal function.  

This project will combine biochemical and genetic approaches with electrophysiology and methods for high-end imaging. We expect this project to redefine our understanding of how multiple signalling pathways, working at different time scales and regulating distinct elements of plasticity, integrate at the synapse.

622
Category:
Neuroscience
Project:

Data science approaches to understanding and predicting psychiatric outcomes

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

Dr. Graham Murray

University:
Cambridge
Project Details:

The student will take a clinical informatics or bioinformatics approach to investigate causes and/or outcomes in mental disorder and/or related brain phenotypes. This could involve using GWAS summary statistics for metabolomics, genomics and proteomics and relating these to mental disorder and /or brain phenotypes, using techniques such as statistical genomics and mendelian randomisation. It could also or alternatively involve clinical data from electronic health records, in combination with biomarker data,, with a focus on psychosis and/or depression and possible relation to physical health (cardio-metabolic or immune mechanisms).

621
Category:
Neuroscience
Project:

Characterising changes in median eminence myelination across the spectrum of body adiposity using advanced quantitative magnetic resonance imaging

Project Listed Date:
Institute or Center:
National Institute on Aging (NIA)
NIH Mentor:

Dr Mustapha Bouhrara

University:
Cambridge
Project Details:

Extensive work from the Blouet lab has recently characterised the high level of myelin plasticity in the median eminence (ME), with rapid local turnover of myelin in healthy adult rodents. The ME is a region of the hypothalamus essential for various homeostatic functions, neuroendocrine output and energy balance regulation. Both weight loss, achieved through caloric restriction, and weight gain, obtained by feeding with a high fat diet, reduce ME myelin turnover, leading to local hypo- or hypermyelination, respectively. However, the contribution of changes in ME myelin plasticity and myelination to the behavioural, metabolic, or neuroendocrine adaptations engaged during energetic challenges remains unclear and how these adaptations might be impaired in aging is unknown. Investigating whether similar changes occur in humans requires novel strategies to image ME myelin in vivo in humans with high resolution and sensitivity. In this project, we propose to develop advanced magnetic resonance imaging (MRI) methodologies to perform longitudinal quantifications of ME myelination in young or aged rodents exposed to a variety of genetic or environmental perturbations modifying energy balance and adult myelin plasticity. We will also translate protocols to image and quantify ME myelin in human participants and determine the effect of age and variations across the spectrum of body mass index on ME myelin density. This project will benefit from the expertise available in Dr. Bouhrara in myelin imaging using advanced MRI methodologies to quantify ME myelination in the rodent brain in vivo and in human participants with high neuroanatomical resolution and sensitivity. These optimized protocols will be used in the Blouet lab to investigate long term changes in myelination during homeostatic and metabolic challenges. This is a unique opportunity to bridge the gap between molecular neuroscience and MR physics to address outstanding mechanistic questions regarding metabolic dysfunctions and myelination patterns. We expect that this synergetic work will form the basis for further preclinical investigations and clinical trials of targeted metabolic interventions. 

618
Category:
Neuroscience
Project:

Embryonic vs adult neurogenesis: Do different birth dates lead to functional diversity?

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

Dr. Elisa Galliano

University:
Cambridge
Project Details:

A crucial aspect of brain development and function is that neurons can structurally and functionally modify themselves and the strength of their connections with other neurons in response to certain stimulus patterns. These changes pertain to three main classes of plasticity: synaptic intrinsic, and structural. In the olfactory circuit, structural plasticity is taken to an extreme: not only neurons can change size and shape of neuronal sub compartments, but quite a few neuronal subpopulations can regenerate throughout life, adding and removing entire elements of the circuit (Lledo et al 2006 PMID: 16495940). Among these regenerating cells are olfactory sensory neurons in the nasal epithelium, dopaminergic cells and granule cells in the olfactory bulb, and interneurons in the olfactory cortex. While adult-born neurons have long been believed to be a like-for-like replacement of embryonic-born ones, recent work focusing on bulbar dopaminergic neurons has challenged this view. Indeed, embryonic and postnatally-born dopaminergic cells differ in morphology, function and activity-dependent plasticity (Galliano et al 2018 PMID: 29676260; Galliano et al 2021 PMID: 33483429).

Using transgenic mouse models, immunohistochemistry, electrophysiology, and behavioural testing, this project wants to expand on these findings. Specifically it wishes to investigate:
(a) whether these differences based on birth date seen in the dopaminergic population can be generalized to the other regenerating populations in the olfactory system, and
(b) what behavioural roles do embryonic and regenerating cells play in olfactory processing.

615
Category:
Neuroscience
Project:

The impact of maternal obesity in pregnancy on offspring brain development

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

Prof. Laura Dearden

University:
Cambridge
Project Details:

Maternal over-nutrition and obesity during pregnancy is known to have long-term effects on the health of the offspring, including increased risk of obesity. Weight gain in offspring exposed to maternal over-nutrition is at least in part caused by hyperphagia- implicating altered function of hypothalamic energy homeostatic pathways as an underlying cause- but the precise mechanisms by which the in utero environment impacts on hypothalamic development is unclear. Key metabolic hormones such as insulin, leptin and ghrelin have a dual role during brain development as growth factors. These metabolic hormones are altered in an obese pregnancy, providing a direct route by which the maternal nutritional state can impact on offspring hypothalamic development. We will use a combination of in vivo manipulation of hormone levels (e.g. fetal brain injection) and ex vivo neuro-developmental techniques (e.g. neurospheres) to examine the consequences of altered metabolic hormone levels for early hypothalamic development. We will also use immunofluorescence and viral tracing to study hypothalamic architecture in the offspring of obese mothers once they reach adulthood, and correlate the anatomy with functional readouts of complex feeding behaviours using operant and metabolic chambers.  

614
Category:
Neuroscience
Project:

Assessing the disease severity in CADASIL using patients iPSC-derived models of the neurovascular unit 

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

CADASIL is a hereditary cerebral small vessel disease caused by mutations in the NOTCH3 gene. Small vessel diseases affect the small penetrating arteries and brain capillaries and patients often suffer of migraine, ischaemic stroke, and cognitive decline. Despite its severity, no disease-modifying treatments are available to date. Classical pathogenic mechanisms are associated with cysteine gain or loss in NOTCH3 extracellular domain, but recent studies suggest that mutation site and other polygenic influences may affect disease severity.  In the lab, we have developed a human in vitro model using induced pluripotent stem cells (iPSC) from CADASIL patients to identify new modifying factors which can be targeted therapeutically. The main aim of the project is to establish iPSC models of CADASIL patients with mild and severe phenotype recruited at the Cambridge Stroke clinic and use these models for omics analysis, mechanistic studies, and drugs screening. The project includes a number of techniques: 2D and 3D iPSC-based neurovascular unit models, transcriptomic, proteomic, phenotypic and functional cell assays and high-throughput screening.

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