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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.

34 Search Results

433
Category:
Neuroscience
Project:

The developmental and adult plasticity of thalamocortical connectivity during active learning

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

Dr. Soohyun Lee

UK Mentor:

Prof. Randy Bruno

University:
Oxford
Project Details:

During development, brains grow rapidly as behaviors develop. Impairment in early brain development often leads to neurodevelopmental conditions, including a number of neuropsychiatric disorders. From early postnatal period throughout adulthood, learning leads to important and dynamic changes in brain circuitry, and in an animals’ behaviors to adapt and sense the environment. The hierarchical yet reciprocal interaction between thalamus and cortex is one of the key brain circuits that are involved in learning-related changes from early development to adulthood.

To investigate the development of thalamocortical connection in the context of sensory learning, this project aims to understand 1) the specificity and plasticity in the interaction between thalamus and cortex during both early development and later life, and 2) how the impairment in this functional connection during early development results in long lasting effects on the capacity for learning in the adult brain. Specifically, we will study how different neuronal types and neuromodulators play a role in the developmental and adult plasticity of thalamocortical connectivity.

To address these questions, we will use the rodent whisker-related sensory-motor system because it is ecologically relevant and critical to the animal’s abilities to navigate and engage in goal-directed behavior. We will apply a multidisciplinary approach that combines molecular and genetic techniques with in vivo intracellular and extracellular electrophysiology, in vivo longitudinal calcium imaging, viral tracing, optogenetic and pharmacogenetic methods, and quantitative behavior and anatomical analyses.

Lee’s lab at NIH will focus on early developmental studies and Bruno’s lab at Oxford will focus on adult plasticity. The two labs will use complementary approaches. A student working with Drs. Lee and Bruno will have a unique opportunity to learn conceptual perspectives from both labs, as well as a wide range of experimental and analytical methodologies in the field of system neuroscience. 

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.

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.

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.

242
Category:
Neuroscience
Project:

Dissecting the relationship between amyloid structures and cellular dysfunction in human diseases

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

Prof. Janet Kumita

University:
Cambridge
Project Details:

Aggregation in vivo is associated with a wide range of human disorders including Parkinson’s disease, systemic amyloidosis and motor neuron disease. As the process of amyloid formation results in the population of a highly heterogeneous array of different protein conformers, it is extremely difficult to resolve how specific misfolded protein states elicit detrimental cellular responses. We aim to define the structural attributes of these elusive species and to determine their influence on cellular trafficking, homeostasis and cell-to-cell transfer processes, all factors that are crucial in disease progression.

 

Key areas of interest include:
1) Probing how globular proteins form amyloid fibrils
2) How accessory proteins, such as extracellular chaperones, modulate amyloid formation and how this is related to disease pathology
3) The impact of post-translational modifications on amyloid fibril formation
4) How changes in the cellular quality control mechanisms impact on amyloid fibril formation

233
Category:
Neuroscience
Project:

Transcriptional and post-transcriptional dysregulation in ALS

Project Listed Date:
Institute or Center:
National Institute of Neurological Disorders and Stroke (NINDS)
NIH Mentor:
N/A
University:
Cambridge
Project Details:
N/A
231
Category:
Neuroscience
Project:

Understanding neural activity and circuit dynamics

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

Multiple NIH collaborators

University:
Cambridge
Project Details:
  1. Models of ion channel regulation in single cells and small circuits
  2. Modelling robust neuromodulation
  3. Regulation and control of neural activity and circuit dynamics
225
Category:
Neuroscience
Project:

The role of mitochondrial DNA mutations in neurological diseases and aging

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

Mitochondrial DNA (mtDNA) mutations have emerged a major cause of neurological disease and may also contribute to the ageing process – but their origin is not well understood. Remarkably, we have shown that most humans harbour a mixture of mutant and wild-type mtDNA (heteroplasmy) at very low levels. Our aims is to understand how mtDNA mutations arise, how they are inherited, and how they accumulate in specific tissues, particularly in the nervous system. Harnessing this knowledge, we will develop new treatments targeting the mitochondrion.

224
Category:
Neuroscience
Project:

Roles of microglial phagocytosis in neurodegeneration

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

Prof. Guy Brown

University:
Cambridge
Project Details:
N/A
221
Category:
Neuroscience
Project:

Functional analysis of disease genes causing cerebellar disorders

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

Dr. John Hammer

UK Mentor:

Prof. Esther Becker

University:
Oxford
Project Details:

The cerebellum is a fascinating brain structure. While it has traditionally been regarded solely as a regulator of motor function, recent studies have demonstrated additional roles for the cerebellum in higher-order cognitive functions such as language, emotion, reward, social behaviour and working memory. Accordingly, cerebellar dysfunction is linked to motor diseases such as ataxia, dystonia and tremor, as well as cognitive affective disorders such as autism spectrum disorders and language disorders.


We understand surprisingly little about the molecular processes that underlie the formation of the cerebellum and that, when disrupted, lead to disease. The goal of our research is to provide fundamental insights into the genetic, molecular and cellular mechanisms that govern the development and different diseases of the cerebellum with the  ultimate desire to develop novel treatment options for these disorders.


The project will focus on the functional characterization of novel gene mutations causing cerebellar disorders, with particular emphasis on the effects of disease genes on the dendritic arborisation of developing Purkinje cells in the cerebellum. The approach will be multi-disciplinary and employs a variety of methods including functional experiments in cell lines and primary neurons, as well as modelling of identified patient mutations and their effects using stem cells combined with genome engineering. The project is supervised by two experienced investigators with complementary expertise. Research in the Hammer group at NIH will focus on introducing mutations of interest into primary Purkinje cells and to investigate dendritic phenotypes. Research in the Becker group at Oxford will include further functional analyses in Purkinje cells from mutant mouse models, as well as in human induced pluripotent stem cells.


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


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

218
Category:
Neuroscience
Project:

Molecular studies of excitatory and inhibitory CA1 synapses in synaptic plasticity

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

Dr. Wei Lu

UK Mentor:

Prof. Ingo Greger

University:
Cambridge
Project Details:

A balance between neuronal excitation and inhibition is crucial for normal brain physiology; upsetting this balance underlies various brain pathologies. To shed light on the molecular underpinnings of this regulation at the synapse level, this project will investigate the dynamics of glutamate- and GABA-A synapses and receptors in CA1 hippocampus under baseline conditions and in response to synapse potentiation. Specifically, using structural, functional and imaging approaches we will study both, spiny glutamatergic and aspiny GABA-ergic CA1 synapses and associated receptor complexes (AMPA-type glutamate and GABA-A) and how these change at the synapse- and receptor levels in response to LTP (long-term potentiation) induction. Our aim will be to monitor changes of glutamatergic and GABAergic synapses and receptors at pyramidal neurons (glutamate) and/or parvalbumin-positive (PV+) interneurons at various points after LTP induction. We will monitor changes in synapse size and receptor composition using advanced imaging and electrophysiological approaches.

217
Category:
Neuroscience
Project:

Developing novel treatments for children with inherited neurological diseases

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

Dr. Rita Horvath

University:
Cambridge
Project Details:

Inherited neurological disorders are disabling, progressive, often fatal conditions, representing an enormous unmet medical need with devastating impacts on affected families, the healthcare system, and the economy. There are no cures and the limited therapies available treat symptoms without addressing the underlying disease.

Next-generation sequencing has facilitated a molecular diagnosis for many inherited neurological disorders, such as mitochondrial diseases and other neuromuscular diseases, which are the focus of this research. The development of targeted therapies requires detailed laboratory investigation of molecular and mutational mechanisms, and a systematic evaluation of well-chosen agents as well as gene and transcript directed strategies using standardized experimental systems. Our research is focusing on understanding the molecular pathogenesis of childhood onset inherited neurological diseases, such as mitochondrial disease and other neuromuscular diseases to develop targeted therapies.

 

Using a translational approach, we aim to
1. understand the clinical course of patients in relation to the underlying disease mechanism
2. delineate the mutational and molecular mechanisms of the molecular defect in the appropriate cell types by developing model systems such as induced neuronal progenitor cells (in vitro) and zebrafish (in vivo)
3. improve the treatment options for patients by developing novel therapies that are directed at these mechanisms, including directly at the genetic mutation or resulting transcript.

We use a combination of exome sequencing, genome sequencing, and other omics technologies to identify novel disease genes and disease mechanisms. By functional evaluation in vitro (induced neuronal progenitor cells) and in vivo (zebrafish) we confirm pathogenicity and uncover molecular mechanisms of disease. To address the mutational mechanisms, we use gene transfer, splice modulation, allele silencing and CRISPR/cas systems.

206
Category:
Neuroscience
Project:

Stem cells of the aging MS brain

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

Dr. Isabel Beerman 

University:
Cambridge
Project Details:

Primary progressive multiple sclerosis (PPMS) is a chronic demyelinating disease of the central nervous system, which currently lacks restorative therapies. Transplantation of neural stem cells (NSCs) has been shown to promote healing of the injured CNS, but previous work has demonstrated that NSCs from patients with PPMS are prematurely senescent. Cellular senescence causes a pro-inflammatory cellular phenotype that impairs tissue regeneration. Senescence in PPMS NSCs was found to be associated with increased secretion of HMGB1, a pro-inflammatory alarmin found to inhibit oligodendrocyte differentiation, and also found increased within white matter lesions of PPMS autopsy tissue. This project aims to understand the role of HMGB1 in PPMS NSC senescence using techniques such as CRISPR-Cas9, RNA sequencing, and functional NSC assays. The longterm goal of this project will be to determine the cause of senescence in NSCs from patients with PPMS and if these cells are suitable for therapeutic use.

205
Category:
Neuroscience
Project:

Probing the roles of medial frontal cortical neurons and neuromodulators in decision making

Project Listed Date:
Institute or Center:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
NIH Mentor:

Dr. Andrew Holmes

UK Mentor:

Prof. Armin Lak

University:
Oxford
Project Details:

Andrew Holmes’ Lab (NIH/NIAAA) and Armin Lak’s Lab, Oxford University

Several decades of research has shown that medial frontal cortical neurons, as well as the neuromodulatory system that innervate the medial frontal cortex, notably the dopamine system, are important in reward valuation and decision making. However, it is not known whether different regions of medial frontal cortex play distinct roles in guiding decisions. Moreover, the role of frontal dopamine signals in shaping and regulating decisions has yet to be established. To address these questions, this project will use a combination of large-scale Neuropixels recording across the medial frontal cortex, as well as optical measurement of dopamine release in the medial frontal cortex during decision making in mice. At Oxford, the project will use Neuropixels probes to record the activity of many neurons across different regions of medial frontal cortex while mice perform a task that systematically manipulates the value of choice options. This data will allow us to investigate the relation between frontal neuronal activity and decision-making variables, and characterize distinct roles of different medial frontal regions in choice behavior. At NIH, the project will take advantage of optical and genetic methods to measure the dynamics of dopamine release in frontal cortical regions identified in the electrophysiological recordings. These experiments will reveal the roles that frontal dopamine play during decision making. In analyzing the electrophysiological and optical data, we will use computational models of learning and decision making to relate neuronal signals with trial-by-trial model-driven estimates of decision variables. The project is primarily experimental in nature but will provide an opportunity to develop computational skills. Together, the project will provide fundamental insights into behaviorally-relevant computations that neurons across the medial frontal cortex perform during decision making, and will reveal the roles of frontal dopamine signals in shaping choice behavior. For more information please visit: https://www.niaaa.nih.gov/laboratory-behavioral-and-genomic-neuroscience and https://www.laklab.org.

*This project is available for the 2021 Oxford-NIH Pilot Programme*

188
Category:
Neuroscience
Project:

Neuroimmune mechanisms underlying obesity

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

Prof. Ana Domingos

University:
Oxford
Project Details:

The Domingos laboratory researches neuroimmune mechanisms underlying obesity. We discovered the sympathetic neuro-adipose junction, a functional synapse-like connection between the sympathetic nervous system and white adipocytes (Cell 2015). We found that this neuro-adipose junction is necessary and sufficient for fat mass reduction via norepinephrine (NE) signaling (Cell 2015, Nature Comm 2017). We then discovered Sympathetic neuron-Associated Macrophages (SAMs) that directly import and metabolize NE. Abrogation of SAM function promotes long-term amelioration of obesity independently of food intake (Nature Medicine, 2017). Given the recent discovery of SAMs, virtually nothing is insofar known about the cell biology of these cells or what other immune cells populate the SNS to cross talk with SAMs.

This PhD project aims to uncover  biological mechanisms of SAM biology. Using single cell sequencing methods, the student will unravel the heterogeneity of the sympathetic neuro-immune cross talk involving SAMs. By identifying novel immune cell mediators, we will have a better understanding of how SAMs are regulated, and pave the way to the identification of cellular and molecular targets that would then be amenable to drug delivery. We will be guided by singe cell sequencing dataset for formulating hypothesis that model fundamental aspects regarding the biology of these cells. The interactions between SNS axons and SAMs, or other resident cells identified by single cell sequencing, will be resolved by super resolution microscopy and 3D reconstruction, for a better understanding of the intricate topology of SAMs’ morphology in relation to SNS axons (Nature Medicine 2017). The PhD candidate can also use optogenetics to probe neuro-immune interactions (as in Nature Medicine 2017), as well as 3DISCO imaging for mapping the distribution of the aforementioned cells in adipose tissues. This project will give a candidate a tremendous opportunity to apply cutting-edge methods in the growing field of neuroimmune biology.

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