We study the molecular and cellular biology of pathogenic human viruses to understand how they interact with their host cells. We are particularly interested in the intrinsic host defences encoded by mammals that directly target diverse RNA and DNA viruses, and in turn the mechanisms by which viruses have evolved to overcome them.
We are always seeking talented scientists interested in viruses to join our team. We particularly encourage postdoctoral scientists to contact us informally to discuss potential opportunities.
PhD studentships will be advertised through KCL Doctoral Training Programmes.
People
Post-Doctoral Research Associate
Visiting Research Fellow
Research Associate
Research Associate
PhD Student
Projects
HIV-1 accessory protein function in the pathogenesis of HIV/AIDS.
HIV-1 encodes four accessory proteins, Vif, Vpr, Vpu and Nef, whose role is to promote viral replication in vivo by counteracting cell intrinsic innate immune restrictions and shielding the infected cell from detection by T cells, antibodies and NK cells. We are particularly interested in the roles of Vpr and Vpu. They act early and late in the viral life cycle respectively to suppress antiviral restrictions, proinflammatory signalling and pattern recognition by targeting a range of cellular proteins for ubiquitin-dependent destruction. In addition, we are currently focussing on how their functions play into the establishment and maintenance of latent proviruses in a small subset of CD4+ T cells in vivo that represent the barrier to curing individuals of HIV-1.
Viral envelope glycoprotein structure and resistance to innate immunity (with Prof Sergi Padilla Parra)
An absolute requirement for all enveloped viruses to enter cells is the fusion of their membrane with that of the host. The mammalian innate immune system deploys a range of interferon-induced proteins to make this process more difficult for the virus and thus reduce infection and transmission. In the case of both HIV-1 and SARS-CoV-2 (and therefore probably most enveloped viruses), sensitivity to these factors is modulated by the stability and dynamics of viral glycoprotein as it conformationally transitions to activate its fusion mechanism. We collaborate with the Padilla Parra group to image viral entry at the single molecule level to understand the entry process and how glycoprotein structural integrity confers resistance to innate immunity.
How RNA-directed antiviral proteins discriminate viral and cellular RNA (with Dr Chad Swanson)
A hallmark of vertebrate pattern recognition is the ability of cells to tell the difference between host RNA species and those that may be of viral origin. We work together with the group of Chad Swanson to understand one particularly conserved system governed by the Zinc-finger Antiviral Protein (ZAP) and its essential cofactors, the E3 ubiquitin ligase TRIM25 and the endoribonuclease KHNYN. Using retroviruses, diverse RNA viruses and herpesviruses we seek to understand the molecular mechanism of this pathway, its role in viral pathogenesis, and whether it can be used as a paradigm for how the cell discriminates viral RNA or ‘harmful’ host RNA species at the level of sequence, structure, and subcellular localization.
Evolution of immune evasion in persistent SARS-CoV-2 infections (with Dr Rui Galao and UKRI G2P2 consortium)
As SARS-CoV-2 continues to evolve into new variants that overcome vaccine-mediated protection from infection, key questions arise about how these variants change in their pathogenesis and transmissibility, and where they are being selected in the first place. Investigating these questions is the mission of a UKRI and Wellcome funded consortia of UK and international scientists called the Genotype-2-Phenotype Part 2 (G2P2) and G2P-Global respectively. In collaboration with Dr Rui Pedro Galao and Dr Luke Snell at GSTT, we are studying a cohort of immunocompromised individuals in which SARS-CoV-2 persisted for months or even years. Using long-read nanopore based sequencing, serology and reverse genetics systems we are studying the innate and adaptive immune escape of SARS-CoV-2 in these individuals that generate viral haplotypes highly reminiscent of Variants of Concern that have emerged over the pandemic.
Publications
Lab Alumni
Neil lab postdocs
- Dr Alessandra Calvi
- Dr Anna Le Tortorec
- Dr Rui Pedro Galao
- Dr Toshana Foster
- Dr Gregory Berger
- Dr Pedro Matos
- Dr Kristina Schierhorn
- Dr Sudeep Bhushal
- Dr Claire Kerridge
- Dr Harry Wilson
- Dr Maria Jose Lista (with Chad Swanson)
Neil Lab graduate students
- Dr Raphael Vigan
- Dr Tonya Kueck
- Dr Julia Weinelt
- Dr Jonathan Sumner
- Dr Franka Debeljak
- Dr Harry Wilson
- Dr Helena Winstone
People
Post-Doctoral Research Associate
Visiting Research Fellow
Research Associate
Research Associate
PhD Student
Projects
HIV-1 accessory protein function in the pathogenesis of HIV/AIDS.
HIV-1 encodes four accessory proteins, Vif, Vpr, Vpu and Nef, whose role is to promote viral replication in vivo by counteracting cell intrinsic innate immune restrictions and shielding the infected cell from detection by T cells, antibodies and NK cells. We are particularly interested in the roles of Vpr and Vpu. They act early and late in the viral life cycle respectively to suppress antiviral restrictions, proinflammatory signalling and pattern recognition by targeting a range of cellular proteins for ubiquitin-dependent destruction. In addition, we are currently focussing on how their functions play into the establishment and maintenance of latent proviruses in a small subset of CD4+ T cells in vivo that represent the barrier to curing individuals of HIV-1.
Viral envelope glycoprotein structure and resistance to innate immunity (with Prof Sergi Padilla Parra)
An absolute requirement for all enveloped viruses to enter cells is the fusion of their membrane with that of the host. The mammalian innate immune system deploys a range of interferon-induced proteins to make this process more difficult for the virus and thus reduce infection and transmission. In the case of both HIV-1 and SARS-CoV-2 (and therefore probably most enveloped viruses), sensitivity to these factors is modulated by the stability and dynamics of viral glycoprotein as it conformationally transitions to activate its fusion mechanism. We collaborate with the Padilla Parra group to image viral entry at the single molecule level to understand the entry process and how glycoprotein structural integrity confers resistance to innate immunity.
How RNA-directed antiviral proteins discriminate viral and cellular RNA (with Dr Chad Swanson)
A hallmark of vertebrate pattern recognition is the ability of cells to tell the difference between host RNA species and those that may be of viral origin. We work together with the group of Chad Swanson to understand one particularly conserved system governed by the Zinc-finger Antiviral Protein (ZAP) and its essential cofactors, the E3 ubiquitin ligase TRIM25 and the endoribonuclease KHNYN. Using retroviruses, diverse RNA viruses and herpesviruses we seek to understand the molecular mechanism of this pathway, its role in viral pathogenesis, and whether it can be used as a paradigm for how the cell discriminates viral RNA or ‘harmful’ host RNA species at the level of sequence, structure, and subcellular localization.
Evolution of immune evasion in persistent SARS-CoV-2 infections (with Dr Rui Galao and UKRI G2P2 consortium)
As SARS-CoV-2 continues to evolve into new variants that overcome vaccine-mediated protection from infection, key questions arise about how these variants change in their pathogenesis and transmissibility, and where they are being selected in the first place. Investigating these questions is the mission of a UKRI and Wellcome funded consortia of UK and international scientists called the Genotype-2-Phenotype Part 2 (G2P2) and G2P-Global respectively. In collaboration with Dr Rui Pedro Galao and Dr Luke Snell at GSTT, we are studying a cohort of immunocompromised individuals in which SARS-CoV-2 persisted for months or even years. Using long-read nanopore based sequencing, serology and reverse genetics systems we are studying the innate and adaptive immune escape of SARS-CoV-2 in these individuals that generate viral haplotypes highly reminiscent of Variants of Concern that have emerged over the pandemic.
Publications
Lab Alumni
Neil lab postdocs
- Dr Alessandra Calvi
- Dr Anna Le Tortorec
- Dr Rui Pedro Galao
- Dr Toshana Foster
- Dr Gregory Berger
- Dr Pedro Matos
- Dr Kristina Schierhorn
- Dr Sudeep Bhushal
- Dr Claire Kerridge
- Dr Harry Wilson
- Dr Maria Jose Lista (with Chad Swanson)
Neil Lab graduate students
- Dr Raphael Vigan
- Dr Tonya Kueck
- Dr Julia Weinelt
- Dr Jonathan Sumner
- Dr Franka Debeljak
- Dr Harry Wilson
- Dr Helena Winstone
Our Partners
Group lead
Head of Department, Infectious Diseases