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Latest Publications

Displaying 161 - 180 of 5242
Last updated : 31 March 2023 03:36

Multiomic approaches to understand the pathogenesis of extrapulmonary tuberculosis

Robert Wilkinson


Brian Robertson

Reader in Systems Microbiology, Faculty of Medicine, Department of Infectious Disease, Imperial College London

Tuberculosis is an important disease responsible, in 2019, for 1.4 million deaths worldwide. Fifteen percent of cases occur outside the lungs and of these disease forms, pericardial and meningeal disease are the most severe with mortality ranging from 8-40% or higher[1, 2]. Neither condition is satisfactorily modelled in animals and relatively little in-depth understanding has come from human studies hitherto[3, 1].

Our research programme at Crick is strongly linked to the Wellcome Centre for Infectious Diseases Research in Africa at the University of Cape Town. In South Africa we are conducting two clinical trials of intensified antibiotic therapy for pericardial (IMPI-3, US NIH funded) and CNS (Intense-TBM, EDCTP funded) tuberculosis that will recruit 80 and 228 participants respectively over the next two years. A rich clinical phenotype predicated by the investigational nature of these trials is augmented by access to advanced imaging at the Cape Universities Body Imagining Centre (CUBIC) and we are including both Cardiac MRI to assess sequelae of pericardial disease[4]; and both comprehensive MRI sequences and magnetic resonance spectroscopy (MRS) to non-invasively determine selected brain metabolites (Glutamate and GABA).

Both clinical trials are assembling comprehensive biobanks from both blood and site of disease. These will be used in downstream multi-omic (transcriptomic, proteomic, metabolomic) laboratory analyses that will seek correlates of outcome, HIV-1 co-infection status, and treatment allocation and thereby lead to new understanding of pathogenesis. Specific hypotheses in pericardial tuberculosis centre on relationships between pericardial Mtb-specific T cells, and Mtb-induced markers of host cell death pathways, and bacterial load. These studies benefit collaboration with intramural investigators at the National Institutes of Health, Bethesda, MD, USA. In tuberculous meningitis we have documented enrichment of transcripts associated with neuronal excitotoxicity and cerebral damage leading us to pursue a hypothesis that inflammation sets up detrimental metabolic changes that contribute to brain injury and which may be targeted by novel adjunctive therapies[5]. 

The opportunity exists therefore particularly (but not restricted to) for a Neurologist, Microbiologist, Cardiologist, Microbiologist or Radiologist in training to join the team as a Clinical PhD student. The projects are highly multidisciplinary and multifaceted and the candidate would have ample opportunity to define niche prior to taking up the Fellowship. We envisage training will include ICH-Good clinical practice, clinical trials conduct, non-invasive imaging, Immunology, Bioinformatics, and Metabolomics. COVID-19 travel restrictions permitted, there would be opportunity to join the clinical team in South Africa during the early part of the Fellowship. However, in keeping with the nature of Crick, the bulk of time would be expected in laboratory work in close collaboration with the Bioinformatic, Metabolomic, Biostatistic, Advanced sequencing and Flow cytometric Science Technology Platforms and with our collaborating scientists. Whilst not therefore being prescriptive at the application stage one example project would be the relationship at the single cell (sc) level of T cell phenotype to bacterial load in the pericardium. This can range from being culture negative to containing over 10e6 bacilli/mL. We will have precise quantitative estimates and the ability to sort cells for scRNAseq. Work on peripheral blood has revealed much greater diversity than hitherto. Thus a hypothesis would be that the T cell response associated with no detectable or low bacillary content may differ from that in multibacillary disease and thus provide insight into protective immunity.

The partner institution for this project is Imperial College London.


  1. Howlett, P., Du Bruyn, E., Morrison, H., Godsent, I. C., Wilkinson, K. A., Ntsekhe, M. and Wilkinson, R. J. (2020) The immunopathogenesis of tuberculous pericarditis. Microbes Infect 22: 172-181. PMID 32092538
  2. Wilkinson, R. J., Rohlwink, U., Misra, U. K., van Crevel, R., Mai, N. T. H., Dooley, K. E., et al. (2017) Tuberculous meningitis. Nat Rev Neurol 13: 581-598. PMID 28884751
  3. Davis, A. G., Rohlwink, U. K., Proust, A., Figaji, A. A. and Wilkinson, R. J. (2019). The pathogenesis of tuberculous meningitis. J Leukoc Biol 105: 267-280. PMCID PMC6355360
  4. Matthews, K., Deffur, A., Ntsekhe, M., Syed, F., Russell, J. B., Tibazarwa, K., . . . Wilkinson, K. A. (2015) A Compartmentalized Profibrotic Immune Response Characterizes Pericardial Tuberculosis, Irrespective of HIV-1 Infection. Am J Respir Crit Care Med 192: 1518-1521. PMCID PMC4731721
  5. Rohlwink, U. K., Figaji, A., Wilkinson, K. A., Horswell, S., Sesay, A. K., Deffur, A.,  et al. (2019) Tuberculous meningitis in children is characterized by compartmentalized immune responses and neural excitotoxicity. Nat Commun 10: 3767. PMCID PMC6704154
5 A PhD project for the 2022 doctoral clinical fellows programme with Robert Wilkinson (primary supervisor) and Brian Robertson (Imperial College London) A PhD project for the 2022 doctoral clinical fellows programme with Robert Wilkinson and Brian Robertson On Positions: doctoral clinical fellows Off Off empty Off

Laboratory Research Scientist - Human Embryo and Stem Cell Unit

Submitted by codeenigma-mas… on 20 September 2021

Reports to:

Principle Laboratory Research Scientist

Contact term:

This is a full-time, permanent position on Crick terms and conditions of employment.


The area of pluripotent stem cell research is a dynamic field with a broad scope of applications due to the ability of the cells to differentiate down lineages representative of all three germ layers. Apart from the potential clinical application of human pluripotent stem cells in the field of cell therapies, the use of these cells is well established in areas of assay development, modelling of developmental pathways and disease modelling. The utilisation of these applications coupled with the use of gene editing tools such as CRISPR makes this type of biological system ideal to study the effects of gene knockout or gene modification. The Human Embryo and Stem Cell Unit (HESCU) is a core facility and supports and develops workflows with Crick scientists that involve the use of human pluripotent stem cells. HESCU has a multidisciplinary user base that is dynamic, evolving and expanding and with this comes the opportunity to be involved in cutting edge research.

Project summary

HESCU provides and maintains a well-equipped laboratory space and as a communal lab space, facilitates interaction between the groups working with human pluripotent stem cells fostering collaboration, exchange of ideas and the sharing of protocols between the scientific groups who use the facility. We currently work with users to provide support and promote best practice, in the areas of growing pluripotent stem cells, differentiation, characterisation, banking and method development. In addition, we are involved in the reprogramming of somatic cells to produce pluripotent stem cell lines. We are looking to extend our portfolio to include gene editing technologies to add value to the core service.

We are looking for a motivated, collaborative, scientist to work with HESCU staff and the user base on established protocols and to help maintain and aid in the development of the portfolio of services offered by this core facility.

Key responsibilities

Provision and support for the day to day running of the facility, ensuring effective service delivery. These responsibilities include but are not limited to:


  • Day to day management of stock
  • Cleaning laboratory spaces and equipment
  • Helping with operational activities and planned preventative maintenance

Provision of media and reagents

  • Inventory and stock control
  • Aliquoting reagents
  • Reagent preparation

Quality Control assisting with adopted methods

  • Immunofluorescence,
  •  RT-PCR, Mycoplasma,
  •  DNA and RNA extraction

Expansion of cell lines

  • Banking cell lines
  • Distribution of cell lines to users
  • Cryopreservation of cell lines
  • Thawing cell lines
  • Stability testing
  • Production of feeder cells

Key experience and competencies

The post holder should embody and demonstrate our core Crick values: bold, imaginative, open, dynamic and collegial, in addition to the following:


Qualifications, experience and competencies:

  • Degree in a biological subject
  • Experience in cell culture  
  • Excellent communication and presentation skills.
  • Excellent organisational skills and record keeping with attention to detail
  • A good working knowledge of Microsoft Office and internet skills
  • Ability to prioritise workflows and deliver to deadlines
  • Highly self-motivated with a pro-active approach.
  • Proven ability to work both collaboratively and independently.
  • Accurate record keeping


Qualifications, experience and competencies:

  • Experience in human pluripotent stem cell culture
  • Experience in a range of molecular biology techniques including RT-PCR and Real Time qRT-PCR.
  • Experience in Flow Cytometry and Immunofluorescence
  • Excellent inter-personal skills and a willingness to learn new skills
  • Ability to work with diverse databases 36 1 Lyn Healy Stp |Human Embryo And Stem Cell Unit Team (Lyn Healy) Human Embryonic Stem Cell R433 Search engines may index Yes Science 3 <p>Competitive with benefits, subject to skills and experience</p>

Postdoctoral Training Fellow x2

Submitted by codeenigma-mas… on 4 October 2021

This is a full-time, fixed term (4 years) position on Crick terms and conditions of employment.


The research group

We are a highly interactive, international group of postdoctoral scientists, clinical and non-clinical PhD students leading research into cancer metabolism. We look forward to welcoming new members who share our passion to understand cancer metabolism and to identify vulnerabilities in these pathways as targets for therapy.

Project summary

Our lab has made major contributions to understanding how nutrient availability, metabolism and ROS regulation impact cancer initiation and progression. We have recently been awarded an ERC grant to study the metabolic mechanisms underpinning obesity-driven pancreatic cancer by defining the metabolic crosstalk between the adipocytes in the tumour environment and the tumour cells themselves. Using metabolomic profiling, isotope tracing analysis and mouse models, the project aims to understand how adipocytes, the modulation of oxidative stress and formate metabolism affect adipocyte-cancer interactions. For this project we are seeking postdoctoral fellows who will make use of a wide range of techniques, including metabolomics, cell biology and mouse studies. We need dedicated, ambitious, creative and collaborative scientists with previous experience in cancer cell biology, mouse models of obesity or pancreas cancer and cancer cell or systemic metabolism. Postdoctoral Training Fellows are expected to be self-motivated and independently drive this own research projects, while also contributing to other projects on a collaborative basis (both in the lab and with external collaborators) and guide PhD students in their research.

Key experience and competencies

The post holder should embody and demonstrate our core Crick values: bold, imaginative, open, dynamic and collegial, in addition to the following:


  • PhD in the area of cancer biology or metabolism or in the final stages of PhD submission
  • High degree of proficiency in at least one of the following areas
  • Metabolic pathways – expertise in lipid metabolism is a bonus
  • Systemic metabolism in mice
  • Cancer models and the analysis of tumour/host interactions
  • Technical metabolomic analysis
  • Expertise in cell and molecular biology
  • Track record of writing papers as evidenced by publications or submitted manuscripts in refereed journals
  • Evidence of data presentation at scientific meetings
  • Experience of experimental design
  • Ability to work independently and also capable of interacting within a group 36 2 Karen Vousden Karen Vousden Vousden K |Research Group - 2 (Karen Vousden) Karen Vousden R421 Search engines may index Yes Science 4 <p>Competitive with benefits, subject to skills and experience.</p>

Digital Project Manager

Submitted by codeenigma-mas… on 21 September 2021

This is a part-time (3 days per week), temporary position (24 months) on Crick terms and conditions of employment.



We are seeking an experienced and creative digital project manager to lead on expanding the Crick’s public engagement work into digital channels.

Building on successful public events, exhibitions and education outreach programmes, the project is part of a 5-year, £1.2m initiative which includes expanding and improving our digital offer to engage people with Crick science.

This exciting role will lead both the discovery and delivery work needed to better engage public audiences, presenting an opportunity for a creative, strategic thinker to steer the digital public engagement work of a world-class scientific institute for the coming years.

We anticipate that a large part of the project will be the design and delivery of a new public-facing section of our website, along with a strategy for how to integrate this with content on existing and prospective channels.

This post sits within the Communications and Public Engagement team, which leads on the Crick’s strategic priority of engaging and inspiring the public. The successful candidate will also work closely with colleagues in the Crick’s Software Development team, as well as external contractors including developers, designers, content producers, marketing specialists, evaluators and other internal and external stakeholders.

We are looking for someone with significant experience managing digital projects, ideally within an academic or cultural context. The successful candidate will be highly motivated and organised, with a commitment to the principles and practice of equality, diversity and inclusion.

Key responsibilities

The main objective of the role is to manage a project to expand and improve the Crick’s digital offer for public audiences, including the successful delivery of a new public-facing section of our website.

Specific responsibilities will include, but not be limited to, the following: 

  • Manage the strategic development and delivery of the Crick’s digital engagement offer, extending our public engagement activities to reach new audiences through digital channels.
  • Lead on the project management of a new public-facing section of our website and wider digital offering from inception to delivery, collaborating with members of the Communications, Public Engagement and Software Development teams, and bringing in new contractors as required.
  • Build on existing work to define overall objectives and specific deliverables required to complete the project, and creating a prioritised roadmap of activity.
  • Liaise with internal and external stakeholders, including technical and business stakeholders, to ensure that the project is delivered on time and on budget.
  • Work with the Digital Communications Content Manager, Head of Public Engagement, and development teams to identify, recruit and manage external agencies and/or contractors to support the delivery of the project.
  • Manage a budget to deliver the project, coordinating invitation to tender processes in collaboration with the Procurement team, and negotiating contracts with support from the Legal team.
  • Coordinate internal stakeholder management, including requirements gathering and sign-off.
  • Prepare for, deliver and record project meetings, such as steering committee meetings, and project team meetings.
  • Work with colleagues in the Crick’s Public Engagement and Communications teams to build a strategic and sustainable approach to digital engagement.
  • Participate in discussions concerning brand, marketing and evaluation strategies.
  • Support other digital engagement projects where necessary and relevant.
  • Champion Agile practices within the project and wider team, including iterative development, and a test and learn approach.
  • Undertake training if necessary to become the online safeguarding coordinator, ensuring that any digital engagement activity is developed in line with our values and within the law, and developing processes which allow us to respond appropriately to any incidents.
  • Uphold and promote the Crick’s commitment to equality, diversity and inclusion (EDI); and actively contribute to an inclusive workplace culture.
  • Work with colleagues to strategically embed EDI principles and practice in our public engagement programmes, ensuring our activities are as inclusive and accessible as possible.

Key experience and competencies

The post holder should embody and demonstrate our core Crick values: bold, imaginative, open, dynamic and collegial, in addition to the following:


Qualifications, experience and competencies:

  • Significant experience managing digital projects from concept to creation.
  • Strong knowledge of both Agile and traditional project management principles with the ability to blend them together in the right proportions to fit a project.
  • Proven track record of delivering projects on time and on budget, and experience of leading a tender process.
  • Experience of successfully running projects with multi-functional project teams including developers, user experience designers, content editors and visual designers.
  • Demonstrable and in depth understanding of products and technologies in the digital/web space.
  • An appreciation of good practice in engaging public audiences using digital formats, ideally within an academic, science engagement, or cultural context.
  • Excellent communication skills, with the ability to engage and build relationships with a range of stakeholders.
  • High levels of self-motivation, with the ability to work within an environment subject to change.
  • Excellent understanding of usability and accessibility standards, and GDPR compliance.
  • Hands on experience with content management systems, including Drupal.
  • A good understanding of the principles and practice of equality, diversity, and inclusion (EDI) and how they relate to developing inclusive and accessible digital engagement experiences.


Qualifications, experience and competencies:

  • A project management qualification, either in Agile or Prince2.
  • Experience of project managing Drupal development projects.
  • Experience managing user research and testing projects.
  • In-depth understanding of digital analytics, including reporting tools such as Google Analytics, email marketing, and content optimisation tools such as HotJar.
  • Experience of developing and delivering digital engagement projects for public audiences from scratch.
  • An understanding of good practice in online safeguarding.

About us

The Francis Crick Institute is a biomedical discovery institute dedicated to understanding the fundamental biology underlying health and disease. Its work is helping to understand why disease develops and to translate discoveries into new ways to prevent, diagnose and treat illnesses such as cancer, heart disease, stroke, infections, and neurodegenerative diseases.

An independent organisation, its founding partners are the Medical Research Council (MRC), Cancer Research UK, Wellcome, UCL (University College London), Imperial College London and King’s College London. 

The Crick was formed in 2015, and in 2016 it moved into a new state-of-the-art building in central London which brings together 1500 scientists and support staff working collaboratively across disciplines, making it the biggest biomedical research facility under a single roof in Europe.

Equality, Diversity & Inclusion

We welcome applications from all backgrounds. We are committed to providing equal employment opportunities, regardless of ethnicity, nationality, gender, sexual orientation, gender identity, religion, pregnancy, age, disability, or civil partnership, marital or family status. We particularly welcome applications from people who are Black, Asian and Minority Ethnic as they are currently underrepresented in the Crick at this level.

Diversity is essential to excellence in scientific endeavour. It increases breadth and perspective, leading to more innovation and creativity. We want the Crick to be a place where everyone feels valued and where diversity is celebrated and seen as part of the foundation for our institute’s success.

The Crick is committed to creating equality of opportunity and promoting diversity and inclusivity. We all share in the responsibility to actively promote dignity, respect, inclusivity and equal treatment and it is our aim to ensure that these principles are reflected and implemented in all strategies, policies and practices.

Read more on our website: 21.6 1 Rosie Waldron Public Engagement Team (Rosie Waldron) R196 Search engines may index Yes Operations 3 <p>F<span>rom £49,500 per annum </span>(pro rata 3 days per week)</p>

ITO Support Engineer

Submitted by codeenigma-mas… on 17 September 2021

Reports to

ITO Helpdesk Manager

This is a permanent position on Crick terms and conditions of employment.


This role will report to the ITO Helpdesk Manager and will be based at the Francis Crick Institute to provide 1/2nd line support. Key responsibilities These include but are not limited to:

  • Working on a shift pattern of 8am – 6pm Mon – Fri in the ITO Helpdesk team, providing a single point of contact service for all Francis Crick employees.
  • Providing 1st and 2nd line ITO support, with primary focus on resolving issues remotely using existing technologies and when necessary by desk visit.
  • Ensuring all technical issues and queries received via phone, email, self-service portal or walk-up are logged, tracked and actioned according to agreed processes and best practice.
  • Providing a service that is responsive to customer needs by solving as many problems as quickly and directly as possible; if necessary, liaising with other ITO staff to complete the resolution of the problems.
  • Participate as required, and as directed by the relevant ITO team members, in the following administrative processes: purchases and asset management (raising orders, monitoring deliveries, returns, etc), recording software licences and managing support contracts for computer hardware and related equipment, general administration and office management.
  • Onboard users as required, including the provisioning of end user devices and the setup of user IT credentials and access to relevant systems.

Key experience and competencies
The post holder should embody and demonstrate our core Crick values: bold, imaginative, open, dynamic and collegial, in addition to the following:

Person Specification

  • Previous experience in an IT helpdesk environment.
  • A proven track record of delivering high quality customer service both in person and on the telephone.
  • A demonstrable ability to prioritise effectively in response to competing demands from customers.
  • A demonstrable ability to “put yourself” in the place of customers and ensure that the service provided is meeting their needs.
  • A “can do” approach to responding to customer queries.
  • Entry level Networking qualification or striving towards.
  • Working knowledge of ITIL best practice for IT support.
  • Good standard of general education, including grade C or above (or equivalent) in GCSE English and Maths.
  • Excellent written and verbal communication skills and attention to detail.
  • Strong organisational skills and a demonstrable ability to manage own time effectively.
  • Strong interpersonal skills and a demonstrable ability to build effective relationships at all levels.
  • Quick learner with proven ability to adapt to changing circumstances.
  • Previous experience of working in science or medical research environments would be an advantage.

Technical Skills

  • Previous experience of using call-logging or job-tracking systems for IT service requests and Incident Management.
  • Previous experience of using ServiceNow an advantage.
  • Demonstrable experience of supporting Apple computers running Mac OS X.
  • Previous experience of troubleshooting both Mac and Windows applications, particularly Microsoft Office 365, Adobe Creative Suite, Virtual Applications, Database connections, Data recovery and OS Patching.
  • Previous experience with using remote software deployment tools, Casper essential.
  • Previous experience of maintaining and troubleshooting IT desktop hardware and software in a networked environment.
  • Previous experience of MS Exchange, Active Directory administration and SharePoint and first line troubleshooting.
  • Experience with MDM and VPN solutions and supporting mobile devices and Tablets, including iOS and Android.
  • Previous experience of supporting and / or setting-up users on telephony using Cisco Call Manager, WebEx and Jabber.
  • Previous experience supporting meeting rooms configuring and troubleshooting video projectors and video conference systems an advantage.
  • Previous experience with Network Patching, including basic knowledge of switch commands and VLANs.
  • Experience building and supporting a mixed Linux environment, predominantly CentOS and Ubuntu.
  • Previous experience supporting hardware on MFD Printers.
  • Experience with deployments, hardware refreshes and desk moves.
  • Knowledge of Linux scripting an advantage.
  • Experience of supporting Scientific Equipment would be an advantage. 36 1 Jude D'Souza Ito Helpdesk Team (Jude D'Souza) R425 Search engines may index Yes Operations 6 <p><span>Competitive with benefits, subject to skills and experience</span></p>