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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.

35 Search Results

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.

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:
N/A
NIH Mentor:
N/A
UK Mentor:

Prof. Esther Becker

University:
Oxford
Project Details:

Our group is interested in the genetic, molecular and cellular mechanisms that underlie disorders of the cerebellum such as cerebellar ataxia but also autism and language disorders.  Ongoing work in our group is aimed to elucidate the underlying pathogenic mechanisms of novel genetic disorders affecting the cerebellum. Our approach is multi-disciplinary and employs a variety of methods including the generation and characterization of novel mouse models, functional experiments in cell lines and primary neurons, as well as modelling of identified patient mutations and their effects using human induced pluripotent stem cells combined with genome engineering.

219
Category:
Neuroscience
Project:

Quantitative methods for analysis of complex brain networks and neuroimaging data

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

Dr. Armin Raznahan

University:
Cambridge
Project Details:

The current project has a core emphasis on quantitative methods for analysis of complex brain networks and neuroimaging data. It will build on our prior work in one of 2 broad directions and will be tailored based on the incoming student’s scientific and training goals:
 

1.       Innovative methods for human brain network mapping, and large-scale applications to population and clinical neuroscience.
The last ten years have witnessed rapid growth in the application of network science to the understanding of human brain organization. Within this framework, the brain is described as a network whose nodes represent large-scale anatomical brain regions and whose links represent structural or functional connections derived from neuroimaging data. We have previously applied these non-invasive macroscopic methods to characterize both adult brain networks and their change during development and ageing, in health and in disease. We are now beginning to develop network-based biomarkers that can help stratify patient populations in clinically useful ways.

To progress this broad agenda, the current project could include for example:

·         Developing new methods to combine structural MRI with additional in vivo imaging modalities (e.g. resting-state functional MRI).
·         Applying novel network-based markers recently developed in our labs to an accelerated longitudinal neuroimaging dataset on adolescence, to uncover how different trajectories of adolescent brain change link to variation in behavior, psychiatric risk and other demographic and societal factors.

 

2.       Novel methods for cross-species or multi-scale data integration.
Developing principled prognostics and interventions will also depend upon our understanding of how microscopic biological mechanisms shape macroscopic brain networks in health and in disease. For example:
·         We recently proposed a "transcriptional vulnerability hypothesis" which posits that the spatial pattern of disease-related brain changes in various psychiatric disorders (measured by MRI) is predicted by expression patterns for disease-relevant genes across the healthy brain. Since many disorders can be best characterized by changes in brain network connectivity, it would be hugely beneficial to develop next-generation neuroinformatic tools that relate disease-specific changes in MRI connectivity (at the edge-level) to gradients in gene expression between pairs of brain regions. This project could form the basis for predictive models of selective brain vulnerability to neuropsychiatric disease.
·         Translational studies of human and animal MRI networks will be crucial to uncovering the biology of mental health disorders. There are a number of opportunities for extending MRI connectomic analyses from human to 9.4T animal imaging (in rodents and marmosets) in the context of development, addiction, anxiety and depressive disorders. Network-level changes in these animal models can then be further investigated with neural, pharmacological, histological and genomic methods.

218
Category:
Neuroscience
Project:

Molecular studies of excitatory and inhibitory CA1 synapses in synaptic plasticity

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

Dr. Wei Li

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.

215
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.

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.

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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