PhD projects and supervisors

Potential PhD projects will have the opportunity to engage in fundamental questions in human thymus biology and T cell development. The projects will explore immune tolerance and contribute to the development of translational approaches for both congenital and chronic disorders, including cancer. Our dynamic and collaborative environment fosters scientific innovation and provides a solid foundation for training junior researchers.

1. Savvidis et al. Advanced three-dimensional X-ray imaging unravels structural development of the human thymus compartments. 2024 Communications Medicine.
2. Reuschl et al. Enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants. Nature Microbiology 2024
3. Ragazzini et al. Defining the identity and the niches of epithelial stem cells with highly pleiotropic multilineage potency in the human postnatal thymus. Developmental Cell 2023
4. Bouhaddou, Reuschl et al. SARS-CoV-2 variants evolve convergent strategies to remodel the host response. Cell 2023
5. Mesner, Reuschl et al. SARS-CoV-2 evolution influences GBP and IFITM sensitivity. Proceedings National Academic of Science 2023 120 (5) e2212577120.
6. Watson et al. Integrated Role of Human Thymic Stromal Cells in Hematopoietic Stem Cell Extravasation. Bioengineering and Translational Medicine 2023 Mar; 8(2): e10454 
7. Campinoti, Gjinovci, Ragazzini et al. Reconstitution of a functional human thymus by postnatal progenitor cells and natural whole organ scaffolds. Nature Communications 2020
8. Claudinot et al. Beyond Lineage Restriction: Tp63-Expressing Adult Epithelial Stem Cells Have Latent Hairy Skin Competence. Nature Communications 2020 Nov 6;11(1): 5645.
9. Park et al. A cell atlas of human thymic development defines T cell repertoire formation. Science 2020, 21;367 (6480).
10. Giobbe et al. Extracellular matrix hydrogel derived from decellularized tissues enables endoderm organoids culture. Nature Communications 2019 Dec 11;10(1): 5658.
11. Bonfanti et al. “Hearts and Bones”: The Ups and Downs of “Plasticity” in Stem Cell Biology. EMBO Molecular Medicine. 2012 May;4(5): 353-61. Review 
12. Bonfanti et al. Microenvironmental Reprogramming of Thymic Epithelial Cells to Skin Multipotent Stem Cells. Nature. 2010 Aug 19;466(7309): 978-82

Potential PhD projects combine wet lab and computational training opportunities. The experimental data use high throughput sequencing to analyse repertoires from a range of clinical sample collections, which include samples from individuals with infectious disease (tuberculosis, HIV and COVID-19), autoimmunity, immunodeficiency, transplantation or cancer. Computational analysis focuses on developing ways to interrogate this data to understand the underlying biology. Specifically we develop methods to compare different TCR sequences, and cluster them in ways which reflect their functional antigen specificity. The goal is to be able to predict the peptide specificity of a T cell receptor from its sequence alone. We are collaborating with Prof. John Shawe-Taylor to apply recent advances in machine learning to protein sequence analysis.

The projects will provide training in immunology, molecular biology and computational biology. The projects will therefore be positioned at the intersection between machine learning and high throughput genomic technologies, which is one of the fastest moving and most exciting areas of the biomedical sciences.

1.    Nagano, Yuta, et al. "Contrastive learning of T cell receptor representations." arXiv preprint arXiv:2406.06397 (2024).
2.    Milighetti et al.  Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection. iScience. 2023 Jun 16;26(6): 106937.
3.    Joshi K, Milighetti M, Chain BM. Application of T cell receptor (TCR) repertoire analysis for the advancement of cancer immunotherapy. Curr Opin Immunol. 2022 Feb;74: 1-8.

In the lab we have generated mouse models in which thymic involution can be reversed in aged mice. As a PhD student you would explore how rejuvenating thymic function alters T-cell subsets within the secondary lymphoid organs and in tissues, following immunological challenge. This will involve flow cytometric phenotyping of different T-cell subsets in multiple tissues and the analysis of single cell RNA sequencing data sets and TCR repertoire analysis. This approach will enable the identification of effector T-cells in older mice with restored thymic function, compared to aged controls and explore differences in their function, transcriptional profiles and repertoire. Overall, the project will explore the effects of aging on T-cells and identify what age-associated changes to T-cells are a consequence of thymic involution.

1. Cowan JE et al, Postnatal Involution and Counter-Involution of the Thymus. Frontiers in Immunology. 2020 May 12.
2. Cowan JE et al. Myc Controls A Distinct Transcriptional Program in Fetal Thymic Epithelial Cells That Determines Thymus Growth, Nature Communications. 2019 Dec 02.
3. Rane S et al. Age is not just a number: Naive T cells increase their ability to persist in the circulation over time. PLoS Biol. 2018 Apr 11.

Project 1: To test the above hypothesis, we are examining how the 3D organization of chromatin, where HIV-1 integrates, influences the virus's ability to enter or exit latency. We have optimized chromosomal conformation capture techniques (HiC) to study changes in chromatin 3D organization upon CD4 T cell activation, along with identifying unique HIV-1 integration sites. We hypothesize that clusters of integration sites located in dynamic 3D chromatin regions represent likely hotspots for reversible latency. These hotspots could be potential targets for selective epigenetic modifiers.

Project 2: Some years ago, we demonstrated that CTVT transmits itself as a cellular parasite. CTVT evades allorecognition during transmission, regardless of the dog's leukocyte antigen type. Nevertheless, it can be rejected by the immune system when the drug vincristine is administered. This extreme bi-modal phenotype is particularly fascinating, as it may provide insights into preventing transplant rejection and triggering the rejection of human cancers. We discovered that vincristine induces CTVT rejection by activating the innate immune system. To understand how a cancer can become transmissible, we have passaged a mouse melanoma in progressively immunologically mismatched mouse strains and obtained an allo-transplantable cancer model. We are using transcriptomics and genomic to study the evolution of this transplantable cancer and the mechanisms that render it able to escape allogeneic rejection.

1. Tomas Raul Wiche Salinas, Yuwei Zhang, Daniele Sarnello, Alexander Zhyvoloup, et al. Th17 cell master transcription factor RORC2 regulates HIV-1 gene expression and viral outgrowth. Proc Natl Acad Sci U S A. 2021; 118(48) e2105927118.
2. Zhyvoloup A, Melamed A, Anderson I, Planas D, Lee CH, Kriston-Vizi J, Ketteler R, Merritt A, Routy JP, Ancuta P, Bangham CRM, and Fassati A. Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. PLoS Pathog. 2017 Jul 20;13(7).
3. Anderson I, Low JS, Weston S, Weinberger M, Zhyvoloup A, Labokha AA, Corazza G, Kitson RA, Moody CJ, Marcello A, Fassati A. Heat shock protein 90 controls HIV-1 reactivation from latency. Proc Natl Acad Sci U S A. 2014 Ap 15;111(15): e1528-37.
4. Murgia C, Pritchard JK, Kim SY, Fassati A, Weiss RA. Clonal origin and evolution of a transmissible cancer. Cell. 2006;126(3): 477-87.
5. Frampton D, Schwenzer H, Marino G, Butcher LM, Pollara G, Kriston-Vizi J,..and Fassati, A. Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor. Cancer Cell. 2018;33(4): 620-33 e6.

Project: The analysis of selection on non-coding regions

Our entire genome, as well as that of all pathogens, is shaped by the process of molecular evolution. In particular, the nucleotide bases and amino acids found in different locations are sculpted by the constraints at those locations, constraints that arise from the function, structure, physiological role, and context at that site. Some important locations must preserve some important property such as size, charge, or hydrogen bonding location. Other locations need to change as the constraints on that site change due to, for instance, a change in function or a change in host. Still other locations in pathogen genomes or immune system genes need to change rapidly so as to avoid causing an effective immune response, or to respond to the changing pathogens. A number of standard approaches have been developed to analysing the strength and nature of the selection (and changes in the selection) in protein-coding genes - one of the most common is to compare the rate of nucleotide substitutions that do or do not result in amino acid changes. These and other methods do not work well in non-coding regions, where there is no amino acid to change. Yet much of the interesting evolutionary dynamics involves changes in non-coding regions such as promoters. There has been increased interest in other non-coding regions as well, including where various RNA molecules are transcribed but not translated into proteins. There is also much interest in the non-coding regions of 'selfish elements' in the genomes such as endogenous retroviruses and other transposable elements. This project would involve developing computational approaches to analyse selection acting on non-coding parts of the genome, including adapting these methods to the study of transposable elements in the genome, and how they are regulated by the host in which they reside.

1. Benjamin P. Blackburne, Alan J. Hay, and Richard A. Goldstein (2008), Changing patterns of selective pressure in Human Influenza H3, PLoS Pathogens, 4, e1000058, PMID: 18451985. 
2. Mario dos Reis, Alan J. Hay, and Richard A. Goldstein (2009), Using Non-Homogeneous Models of Nucleotide Substitution to Identify Host Shift Events: Application to the Origin of the 1918 ‘Spanish’ Influenza Pandemic Virus, J Mol Evol., 69 ,333-345, PMID: 19787384.
3. Asif U. Tamuri, Mario dos Reis, Alan J. Hay, Richard A. Goldstein (2009). Identifying changes in selective constraints: Host shifts in influenza. PLoS Comput Biol., 5, e1000564, PMID: 19911053.
4. Mario dos Reis, Asif U. Tamuri, Alan J. Hay, Richard A. Goldstein (2011). Charting the host adaptation of influenza viruses. Mol Biol Evol 28:1755-1767, PMID: 21109586.
5. Asif U. Tamuri, Mario dos Reis, Richard A. Goldstein (2012). Estimating the distribution of selection coefficients from phylogenetic data using sitewise mutation-selection models, Genetics, 190:1101-1115, PMID: 22209901.

Our lab offers a diverse range of PhD projects, providing students with the flexibility to choose from existing topics or develop their own ideas in alignment with our research focus. We encourage creativity and independent thinking, fostering an environment where students can shape their own scientific journey.

1. Revealing human genetic determinants of virus susceptibility and pathogenicity.

Understanding the host genetic landscape underlying viral infectious diseases provides crucial mechanistic insights and enables the development of personalized therapeutics. This project will integrate structural and functional protein information within a virus-human protein interaction network, leveraging machine learning to identify host genetic variants that may drive disease severity.

2. Develop a unifying computational framework for predicting virus-host protein-protein interactions (PPIs).

Recent advancements in machine learning have revolutionized structural bioinformatics, significantly improving protein and protein complex structure prediction. However, predicting virus-host PPIs remains a challenge due, partly, to limited data. This project will integrate cutting-edge approaches with more traditional approaches to enhance virus-host PPI predictions, bypassing current limitations. While focusing on a specific class of interactions, the framework developed will have broad applications across biology.

3. Characterize the physicochemical properties and evolutionary dynamics of virus-host-protein interfaces.

Viruses have evolved to hijack the host molecular machinery and use it to their advantage by rewiring protein networks. This interaction exerts evolutionary pressure on host proteins, driving them to evade viral interactions while preserving essential cellular functions. What strategies do host proteins adopt to achieve this balance? Can such strategies be leveraged to engineer cellular decoys with therapeutic potential? Conversely, host defenses impose selective pressure on viruses, forcing viral proteins to evolve in response. Does the rapid evolution of viruses and need to interact with multiple cellular partners leave a distinct molecular signature on the binding interfaces of viral proteins?

This project will integrate evolutionary analysis and structural modeling to unravel these dynamics, with potential applications in antiviral development.

4. Engineering therapeutic proteins against viral infectious diseases.

In collaboration with Prof. Kartik Chandran (Albert Einstein College of Medicine, USA), this project will explore innovative strategies to engineer proteins with therapeutic potential against viral infections. We will tackle this challenge from two complementary angles. First, we will integrate structural and evolutionary insights to design tailored libraries of picobodies, cattle-derived antibodies with ultra-long complementary-determining regions (CDRs) that hold promising therapeutic potential. Second, we will refine and expand the neutralizing capabilities of monoclonal antibodies (mAbs) to target a broader spectrum of viral strains or related virus species, enhancing their therapeutic potential.

1. Lasso G, Grodus M, Valencia E, DeJesus V, et al. Decoding the blueprint of receptor binding by filoviruses through large-scale binding assays and machine learning. Cell Host Microbe. 2025 Feb 12;33(2): 294-313.e11.
2. Haslwanter D, Lasso G, Wec AZ, Furtado ND, et al. Genotype-specific features reduce the susceptibility of South American yellow fever virus strains to vaccine-induced antibodies. Cell Host Microbe. 2022 Feb 9;30(2): 248-259.e6.
3. Wells HL, Letko M, Lasso G, Ssebide B, et al. The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus. Virus Evol. 2021 Feb 5;7(1): veab007.
4. Lasso G, Honig B, Shapira SD. A Sweep of Earth's Virome Reveals Host-Guided Viral Protein Structural Mimicry and Points to Determinants of Human Disease. Cell Syst. 2021 Jan 20;12(1): 82-91.e3.
5. Lasso G, Mayer SV, Winkelmann ER, Chu T, et al. A Structure-Informed Atlas of Human-Virus Interactions. Cell. 2019 Sep 5;178(6): 1526-1541.e16.

TPL-2 regulation of innate immune responses to pathogenic bacteria

A key early step in innate immune responses to pathogenic bacteria is the killing of phagocytosed bacteria by macrophages. This involves a process called phagosome maturation, in which internalised bacteria are trafficked into a series of increasingly acidified  embrane-bound vacuoles and then degraded. Recent research by the Ley laboratory has shown that TPL-2 complex stimulates phagosome maturation independently of its established functions in MAP kinase activation (ref 4, below). One PhD project will investigate the importance of this newly discovered regulatory process in innate immune responses to the pathogenic bacteria.

Employing in vitro and in vivo model systems, this will focus on two pathogenic bacterial species :

• Staphylococcus aureus, an extracellular Gram-positive bacterium that is the common cause of pneumonia and the pathogen most frequently linked to health care associated pneumonia.
• Salmonella typhimurium, a Gram-negative pathogen that causes both gastrointestinal and systemic diseases.

TPL-2 regulation of cell survival following HCMV infection

Viruses have proven excellent tools to probe signalling pathways regulating key aspects of cell biology. Our unpublished data suggests that human cytomegalovirus (HCMV) activates TPL-2- ERK1/2 MAP kinase signalling pathway to establish latency in myeloid cells. In collaboration with the Matthew Reeves laboratory, one PhD project will investigate the mechanisms by which HCMV stimulates plasma membrane and endosomal TLR receptors to activate TPL-2 and the downstream consequences of TPL-2 signalling for HCMV infection.

1. Gantke T, Sriskantharajah S, Sadowski M, Ley SC. IκB kinase regulation of the TPL-2/ERK MAPK pathway. Immunol Rev. 2012;246:168 - 82.
2. Pattison MJ, Mitchell O, Flynn HR, Chen C-S, Yang H-T, Ben-Addi A, et al. TLR and TNFR1 activation of the MKK3/MKK6- p38alpha axis in macrophages is mediated by TPL-2 kinase. Biochem J. 2016;473:2845 - 61.
3. Arthur JSC, Ley SC. Mitogen-activated protein kinases in innate immunity. Nature Rev Immunol. 2013;13:679 - 92.
4. Breyer F, Hartlova A, Thurston T, Flynn HR, Chakravarty P, Janzen J, et al. TPL-2 kinase induces phagosome acidification to promote macrophage killing of bacteria. EMBO J. 2021;40:e106188.

If you join our lab you will have your own project on a topical aspect of hepatitis B, liver cancer or SARS-CoV-2 that will interlink with those of the other team members for maximum productivity. We are highly interactive, working closely with staff in a number of clinics to obtain the patient samples so vital to our translational work, as well as with scientific collaborators and a network of consortia here at UCL and internationally.

I have a strong commitment to mentoring and supporting my lab members to obtain fellowships and develop their careers, several of whom now run their own labs alongside mine, with the wonderful help of our lab manager and joint team of technicians.

1. Pallett L.J, Swadling L., Diniz M ... Maini M.K. Tissue CD14+CD8+T-cells are reprogrammed by myeloid cells and modulated by LPS. Nature. 2023 Feb; 614: 334-342
2. Diniz MO, Mitsi E, Swadling L ... Ferreira D*, Maini MK*. Airway-resident T cells from unexposed individuals cross-recognize SARS-CoV-2. Nature Immunol. 2022 Sep;23(9): 1324-1329. *Joint senior authors
3. Diniz MO, Schurich A, Chinnakannan SK ... Maini MK. NK cells limit therapeutic vaccine-induced CD8+T cell immunity in a PD-L1-dependent manner. Science Translational Medicine 2022 Apr13;14(640): eabi4670
4. Swadling L, Diniz MO, Schmidt NM ... Maini MK. Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2. Nature 2022 Jan;601(7891): 110-117
5. Burton AR, Pallett LJ, McCoy LE ... Pelletier N, Maini MK. Circulating and intrahepatic antiviral B cells are defective in hepatitis B Journal of Clinical Investigation 2018 Oct 1;128(10): 4588-4603.

The projects available will aim to investigate:

1. The effect that diet and/or dietary components have on the metabolism of B cells
2. How changes in the gut-microbiota can be harness for the cure of rheumatoid arthritis.

1. Bradford HF, Mauri C. Diversity of regulatory B cells: Markers and functions. Eur J Immunol. 2024 Jul 31:e2350496. doi: 10.1002/eji.202350496.
2. Rosser EC, Mauri C. The emerging field of regulatory B cell immunometabolism. Cell Metab. 2021 Jun 1;33(6):1088-1097. doi: 10.1016/j.cmet.2021.05.008.
3. Oleinika K, Rosser EC, Matei DE, Nistala K, Bosma A, Drozdov I, Mauri C. CD1d-dependent immune suppression mediated by regulatory B cells through modulations of iNKT cells. Nat Commun. 2018 Feb 15;9(1):684. doi: 10.1038/s41467-018-02911-y.

1. Diagnosis and patient stratification in tuberculosis: In our TB research, we have a range of projects that aim to discover novel biomarkers, and integrate these into multivariable models to diagnose prevalent TB disease, predict incident TB disease-risk or provide a test-of-cure that enables implementation of personalised treatment regimens.
2. Tuberculosis immunology: We are particularly interested in identifying the clonal and functional characteristics of protective and pathogenic T cell immunity in TB, by combining TCR sequencing with transcriptional profiling and laboratory models of T cell interactions with Mtb infected macrophages. We aim to identify immunogens that will recruit protective clones for next generation vaccines, and immunological pathways amenable to therapeutic targeting in disease.
3. Diagnosis and patient stratification of acute respiratory virus infections: In our research on respiratory viruses, we have established large observational cohort studies of acute respiratory infections presenting to UK hospitals, in which we combine clinical sampling with high resolution electronic health record data. In these we aim to identify virus agnostic diagnostic biomarkers necessary to improve early detection of viral infection and critical for pandemic preparedness, and biomarkers to identify patients who will benefit from antiviral treatments.
4. Next generation SARS-CoV-2 vaccines: In addition, we work within an international consortium using the SARS-CoV-2 human challenge infection model to develop and test next-generation vaccines that block infection or provide pan-corona virus protection. 

1. Mann T, Minnies S, Gupta RK, Reeve BWP, Nyawo G, Palmer Z, Naidoo C, Doubell A, Pecoraro A, John T-J, Schubert P, Calderwood CJ, Chandran A, Theron G, Noursadeghi M. Blood RNA biomarkers and C-reactive protein for triage of adult patients with tuberculosis lymphadenitis and pericarditis in South Africa: a single-centre, prospective, observational, diagnostic accuracy study. The Lancet Microbe. 2025;0(0). doi:10.1016/j.lanmic.2025.101153.
2. Mann T, Gupta RK, Reeve BWP, Ndlangalavu G, Chandran A, Krishna AP, Calderwood CJ, Tshivhula H, Palmer Z, Naidoo S, Mbu DL, Theron G, Noursadeghi M. Blood RNA biomarkers for tuberculosis screening in people living with HIV before antiretroviral therapy initiation: a diagnostic accuracy study. The Lancet Global Health. April 2024. doi:10.1016/S2214-109X(24)00029-9.
3. Turner CT, Tiffeau-Mayer A, Rosenheim J, Chandran A, Saxena R, Zhang P, Jiang J, Berkeley M, Pang F, Uddin I, Nageswaran G, Byrne S, Karthikeyan A, Smidt W, Ogongo P, Byng-Maddick R, Capocci S, Lipman M, Kunst H, Lozewicz S, Rasmussen V, Pollara G, Knight JC, Leslie A, Chain BM, Noursadeghi M. Evolution of T cell responses in the tuberculin skin test reveals generalisable Mtb-reactive T cell metaclones. bioRxiv. April 2025:2025.04.12.648537. doi:10.1101/2025.04.12.648537.
4. Turner CT, Rosenheim J, Thakker C, Chandran A, Wilson H, Venturini C, Pollara G, Chain BM, Tomlinson GS, Noursadeghi M. Single-cell transcriptome and T cell receptor profiling of the tuberculin skin test. bioRxiv. June 2024:2024.06.25.600676. doi:10.1101/2024.06.25.600676.
5. Pollara G, Turner CT, Rosenheim J, Chandran A, Bell LCK, Khan A, Patel A, Peralta LF, Folino A, Akarca A, Venturini C, Baker T, Ecker S, Ricciardolo FLM, Marafioti T, Ugarte-Gil C, Moore DAJ, Chain BM, Tomlinson GS, Noursadeghi M. Exaggerated IL-17A activity in human in vivo recall responses discriminates active tuberculosis from latent infection and cured disease. Science Translational Medicine. 2021;13(592). doi:10.1126/scitranslmed.abg7673.
6. Gupta RK, Calderwood CJ, Yavlinsky A, Krutikov M, Quartagno M, Aichelburg MC, Altet N, Diel R, Dobler CC, Dominguez J, Doyle JS, Erkens C, Geis S, Haldar P, Hauri AM, Hermansen T, Johnston JC, Lange C, Lange B, van Leth F, Muñoz L, Roder C, Romanowski K, Roth D, Sester M, Sloot R, Sotgiu G, Woltmann G, Yoshiyama T, Zellweger J-P, Zenner D, Aldridge RW, Copas A, Rangaka MX, Lipman M, Noursadeghi M, Abubakar I. Discovery and validation of a personalized risk predictor for incident tuberculosis in low transmission settings. Nature Medicine. October 2020:1-9. doi:10.1038/s41591-020-1076-0.
7. Turner CT, Gupta RK, Tsaliki E, Roe JK, Mondal P, Nyawo GR, Palmer Z, Miller RF, Reeve BW, Theron G, Noursadeghi M. Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study. Lancet Respir Med. 2020;8(4):407-419. doi:10.1016/S2213-2600(19)30469-2.
8. Gupta RK, Turner CT, Venturini C, Esmail H, Rangaka MX, Copas A, Lipman M, Abubakar I, Noursadeghi M. Concise whole blood transcriptional signatures for incipient tuberculosis: A systematic review and patient-level pooled meta-analysis. Lancet Respir Med. 2020. doi.org/10.1016/S2213-2600(19)30282-6.
9. Rosenheim J, Gupta RK, Thakker C, Mann T, Bell LCK, Broderick CM, Madon K, Papargyris L, Dayananda P, Kwok AJ, Greenan-Barrett J, Wagstaffe HR, Conibear E, Fenn J, Hakki S, Lindeboom RGH, Dratva LM, Lemetais B, Weight CM, Venturini C, Kaforou M, Levin M, Kalinova M, Mann AJ, Catchpole A, Knight JC, Nikolić MZ, Teichmann SA, Killingley B, Barclay W, Chain BM, Lalvani A, Heyderman RS, Chiu C, Noursadeghi M. SARS-CoV-2 human challenge reveals biomarkers that discriminate early and late phases of respiratory viral infections. Nat Commun. 2024;15(1):10434. doi:10.1038/s41467-024-54764-3.
10. Chandran A, Rosenheim J, Nageswaran G, Swadling L, Pollara G, Gupta RK, Burton AR, Guerra-Assunção JA, Woolston A, Ronel T, Pade C, Gibbons JM, Sanz-Magallon Duque De Estrada B, Robert de Massy M, Whelan M, Semper A, Brooks T, Altmann DM, Boyton RJ, McKnight Á, Captur G, Manisty C, Treibel TA, Moon JC, Tomlinson GS, Maini MK, Chain BM, Noursadeghi M, COVIDsortium Investigators. Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections. Cell Rep Med. 2022;3(3):100557. doi:10.1016/j.xcrm.2022.100557.
11. Swadling L, Diniz MO, Schmidt NM, Amin OE, Chandran A, Shaw E, Pade C, Gibbons JM, Le Bert N, Tan AT, Jeffery-Smith A, Tan CCS, Tham CYL, Kucykowicz S, Aidoo-Micah G, Rosenheim J, Davies J, Johnson M, Jensen MP, Joy G, McCoy LE, Valdes AM, Chain BM, Goldblatt D, Altmann DM, Boyton RJ, Manisty C, Treibel TA, Moon JC, Dorp L van, Balloux F, McKnight Á, Noursadeghi M, Bertoletti A, Maini MK. Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2. Nature. November 2021:1-10. doi:10.1038/s41586-021-04186-8.
12. Li HK, Kaforou M, Rodriguez-Manzano J, Channon-Wells S, Moniri A, Habgood-Coote D, Gupta RK, Mills EA, Arancon D, Lin J, Chiu Y-H, Pennisi I, Miglietta L, Mehta R, Obaray N, Herberg JA, Wright VJ, Georgiou P, Shallcross LJ, Mentzer AJ, Levin M, Cooke GS, Noursadeghi M, Sriskandan S. Discovery and validation of a three-gene signature to distinguish COVID-19 and other viral infections in emergency infectious disease presentations: a case-control and observational cohort study. The Lancet Microbe. 2021;0(0). doi:10.1016/S2666-5247(21)00145-2.
13. Gupta RK, Rosenheim J, Bell LC, Chandran A, Guerra-Assuncao JA, Pollara G, Whelan M, Artico J, Joy G, Kurdi H, Altmann DM, Boyton R, Maini M, McKnight A, Lambourne J, Cutino-moguel T, Manisty C, Treibel TA, Moon JC, Chain B, Noursadeghi M, COVIDsortium investigators. Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study. The Lancet Microbe. 2021. doi:10.1016/S2666-5247(21)00146-4.
14. Gupta RK, Harrison EM, Ho A, Docherty AB, Knight SR, van Smeden M, Abubakar I, Lipman M, Quartagno M, Pius R, Buchan I, Carson G, Drake TM, Dunning J, Fairfield CJ, Gamble C, Green CA, Halpin S, Hardwick HE, Holden KA, Horby PW, Jackson C, Mclean KA, Merson L, Nguyen-Van-Tam JS, Norman L, Olliaro PL, Pritchard MG, Russell CD, Scott-Brown J, Shaw CA, Sheikh A, Solomon T, Sudlow C, Swann OV, Turtle L, Openshaw PJM, Baillie JK, Semple MG, Noursadeghi M; ISARIC4C Investigators. Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19: a prospective cohort study. Lancet Respir Med. 2021 Jan 11:S2213-2600(20)30559-2. doi: 10.1016/S2213-2600(20)30559-2.

If you would like to join us in the Pallett lab, you will have the opportunity to work on a dynamic project to unravel bits of the cellular 'conversations' occurring within the human liver.

The project will involve working closely with our clinical colleagues to obtain high-quality tissue samples, and exciting state-of-the-art technologies, such as multiplex imaging, spectral flow cytometry and the generation of novel 3D cell-culture systems (to mimic the fibrotic liver in vitro).

The project will be co-supervised by myself and Prof. Mala Maini so you would become part of a highly productive multi-disciplinary team with a fantastic track record of supervision and fun.

1. Pallett L.J. et al. Nature (2023) 'Tissue CD14+CD8+ T cells reprogrammed by myeloid cells and modulated by LPS'
2. Pallett L.J. et al. JEM (2017) 'IL-2high tissue-resident T cells in the human liver: Sentinels for hepatotropic infection'
3. Gill U.S. & Pallett L.J. et al. Gut (2019) 'Fine needle aspirates comprehensively sample intrahepatic immunity'
4. Pallett L.J. & Burton A.R. et al. JEM (2020) 'Longevity and replenishment of human liver-resident memory T cells and mononuclear phagocyte'
5. Ichikawa T. et al. Nat Immunol (2019) 'CD103hi Treg cells constrain lung fibrosis induced by CD103lo tissue-resident pathogenic CD4 T cells'

Available projects include:

• Identification of novel therapeutic targets and/or predictive biomarkers: This project involves integration of ‘omic technologies’ to infer regulatory networks and drivers of immunity and ongoing inflammation in distinct anatomical compartments in patients with HIV and CMV coinfection. This high-resolution strategy will enable patient monitoring and stratification for therapeutic interventions to prevent comorbidities associated with premature ageing.
• Development of NK based cellular therapeutics: Develop a scalable platform for the expansion of adaptive NK cells with enhanced functionality and predictable selectivity. Genetic engineer human NK cells with features that improve their capacity to recognise and kill HIV- and HBV-infected target cells (in collaboration with Waggoner Lab, USA). This approach could circumvent many of the limitations inherent to the current immunotherapeutic approaches as a novel therapeutic avenue for viral disease.
• HIV related immunosuppression and responses to SARS-CoV-2: There is currently little information on vaccine efficacy/correlates of protection in this vulnerable population group. This work will examine the development of specialised NK cell populations exhibiting memory-like features in response to natural infection and vaccination with implications for the development of new vaccine targets.

1. Touizer E, Alrubayyi A, Rees-Spear C, Fisher-Pearson N, Griffith S, Muir L, Pellegrino P, Waters L, Burns F, Kinloch S, Rowland-Jones S, Gupta K R, Gilosn R, Peppa D, McCoy L. Failure to seroconvert after two doses of BNT162b2 SARS-CoV-2 vaccine in uncontrolled HIV infection. Lancet HIV May 2021.
2. Aljawharah Alrubayyi, Ester Gea-Mallorquí, Emma Touizer, Dan Hameiri-Bowen, Jakub Kopycinski, Bethany Charlton, Natasha Fisher-Pearson, Luke Muir, Annachiara Rosa, Chloe Roustan, Christopher Earl, Peter Cherepanov, Pierre Pellegrino, Laura Waters, Fiona Burns, Sabine Kinloch, Tao Dong, Lucy Dorrell, Sarah Rowland-Jones, Laura E. McCoy, Dimitra Peppa. Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV. Nat Commun 12, 5839 (2021). https://doi.org/10.1038/s41467-021-26137-7
3. Gupta RK, Abdul-Jawad S, McCoy LE, Mok HP, Peppa D, Salgado M, Martinez-Picado J, Nijhuis M, Wensing AMJ, Lee H  et al. HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Nature 2019 10.1038/s41586-019-1027-4.
4. Maini MK and Peppa D. Shared immunotherapeutic approaches in HIV and HBV: Combine and Conquer. Current Opinion in HIV and AIDS. 2020 
5. Bradley T, Peppa D, Pedroza-Pacheco I, Li D, Cain DW, Henao R, Venkat V, Hora B, Chen Y, Vandergrift NA, Overman RG, Edwards RW, Woods CW, Tomaras GD, Ferrari G, Ginsburg GS, Connors M, Cohen MS, Moody MA, Borrow P, Haynes BF. RAB11FIP5 expression and altered natural killer cell function are associated with induction of HIV broadly neutralizing antibody responses, Cell 2018 Oct 4;175(2): 387-399e17.
6. Peppa D, Pedroza-Pacheco I, Pellegrino P, Williams I, Maini MK, Borrow P. Adaptive Reconfiguration of Natural Killer Cells in HIV-1 Infection. Front Immunol. 2018 Mar 16;9: 474.
7. Peppa D, Gill US, Reynolds G, Easom NJ, Pallett LJ, Schurich A, Micco L, Nebbia G, Singh HD, Adams DH, Kennedy PT, Maini MK. Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion. J Exp Med. 2013 Jan 14;210(1): 99-114.

CD96, CD226 and TIGIT co-receptor family as immune regulators

• Functional differences between CD96 variants 
• Receptor-receptor-ligand interaction
• Co-receptor intracellular receptor trafficking/signalling upon ligation
• Role of co-receptors in Treg function

Treg gene signature as measure of Treg fitness

• Utilizing the Treg gene and protein signatures as biomarker for disease activity
• Understanding how the Treg signature genes/proteins define Treg fitness functionally
• Can Treg-targeted therapeutic approaches re-set Treg signatures?

Notably, any project will directly contribute to ongoing work in the Pesenacker lab and projects are subject to change and can be personalised. For more information, do not hesitate to get in touch.

1. Attrill MH, Shinko D … Pesenacker AM. Treg fitness as a biomarker for disease activity in Juvenile Idiopathic Arthritis. bioRxiv. 2024:2024.04.24.590917. (2024). DOI: 10.1101/2024.04.24.590917
2. Attrill MH, Shinko D … Pesenacker AM. The immune landscape of the inflamed joint defined by spectral flow cytometry. BioRxiv. 2023:2023.11.30.569010. (2023). DOI: 10.1101/2023.11.30.569010
3. Pesenacker AM, et al. Treg gene signatures predict and measure type 1 diabetes trajectory. JCI insight. 2019;4(6). DOI: 10.1172/jci.insight.123879
4. Pesenacker AM, et al. A Regulatory T-Cell Gene Signature Is a Specific and Sensitive Biomarker to Identify Children With New-Onset Type 1 Diabetes. Diabetes. 2016;65(4):1031-9. DOI:10.2337/db15-0572
5. Lam, AJ et al. Optimized CRISPR-mediated gene knockin reveals FOXP3-independent maintenance of human Treg identity. Cell reports 36, 109494 (2021).

Host and Viral molecular determinants of HCMV latency and reactivation

Latency and reactivation reflects a 'molecular dance' with the cell. Our current research is aimed at understanding key cellular signalling pathways that dictate the latent/reactivation switch and, by extension, the role a subset of viral gene products play in controlling this. Our current major interest is on a virally encoded deSUMOylase activity (LUNA) we characterised as an antagonist of innate immunity. We hypothesise the enzymatic activity of LUNA provides HCMV with the capacity to manipulate multiple host processes providing a fundamental tool to study host cell biology.

The immune response to HCMV and vaccination

HCMV dedicates over 40% of its 230kb genome to immune evasion strategies – enabling it to counter a prodigious host immune response. We are interested in the aspects of that response which are potently anti-viral to learn more about the control of chronic infections in vivo and help guide our ongoing efforts to develop an urgently needed vaccine against HCMV.

HCMV as a tool to understand haematopoiesis

HCMV establishes latency in pluripotent bone marrow progenitors yet is selectively carried in the cells of the myeloid lineage. Thus we are using HCMV as a tool to understand the fundamental mechanisms that promote myeloid cell commitment complementing systems level approaches (scRNAseq, ATACseq) with reductionist studies to describe the phenotype and dissect the mechanisms involved.

More about the lab

1. Mason et al (2023) J. Gen. Virol. 104(9)
2. Gomes A. et al (2023) J. Gen. Virol. 104(6)
3. Murray M. et al (2023) J. Biol. Chem. 299(6):104727
4. Forrest C. et al (2023) Nature Comms. 14(1):1409
5. Gomes A.  et al (2023) Nature Comms. 14(1):1041
6. Mason R et al (2020) J. Gen. Virol. 101(6):635-44
7. Murray M.J. et al (2020) J. Virol. 94 (7):e02012-19
8. Baraniak, I. et al (2019) Lancet EBioMedicine 50:45-54
9. Dupont L. et al (2019) J. Biol. Chem. 294(35):12901-1291
10. Baraniak I. et al (2019) J. Inf. Dis. 220(2):228-232
11. Poole E.L. et al (2018) Cell Reports 24(3):594-606
12. Baraniak I et al (2018) PNAS 115(24):6273-6278

Potential PhD project areas include:

1. Studying the impact of patient-derived mutations in CTLA-4, CD80 and CD86 pathways.
2. Investigating the differential functions of CD80 and CD86 in immune responses.
3. Understanding the molecular mechanism of Transendocytosis.

1. Qureshi, O.S., et al. (2011). Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science 332, 600-603.
2. Schubert, D., et al. (2014). Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nature Medicine 20, 1410-1416.
3. Soskic, B., et.al., (2014). A Transendocytosis Perspective on the CD28/CTLA-4 Pathway. Adv Immunol 124, 95-136.
4. Walker, L.S., and Sansom, D.M. (2015). Confusing signals: Recent progress in CTLA-4 biology. Trends in immunology 36, 63-70.
5. Hou, T.Z. et.al.,(2015). A Transendocytosis model of CTLA-4 function predicts its suppressive behaviour on regulatory T cells. J Immunol 194, 2148-2159.
6. Sansom, D.M. (2015). Moving CTLA-4 from the trash to recycling. Science 349, 377-378.

The PhD project will augment ongoing studies and provide training in molecular, cellular and/or computational immunology. The Seddon laboratory is located in the newly opened Institute of Immunity and Transplantation at the Royal Free Hospital, that offers state of the art facilities and training environment.

The Seddon laboratory has an excellent track record of PhD student training - all students finish with one or more first author papers.

Example Papers from past PhD students (marked in bold)

1. F. Carty, S. Layzell, A. Barbarulo, F. Islam, L.V. Webb, and B. Seddon. 2023. IKK promotes naive T cell survival by repressing RIPK1-dependent apoptosis and activating NF-kappaB. Sci Signal 16:eabo4094.
2. Verheijen, M., S. Rane, C. Pearson, A.J. Yates, and B. Seddon. 2020. Fate Mapping Quantifies the Dynamics of B Cell Development and Activation throughout Life. Cell Rep 33:108376.
3. Webb, L.V., A. Barbarulo, J. Huysentruyt, T. Vanden Berghe, N. Takahashi, S. Ley, P. Vandenabeele, and B. Seddon. 2019. Survival of Single Positive Thymocytes Depends upon Developmental Control of RIPK1 Kinase Signaling by the IKK Complex Independent of NF-κB. Immunity 50:348-361.e344.
4. Webb, L.V., S.C. Ley, and B. Seddon. 2016. J Exp Med 213:1399-1407.
5. Schim van der Loeff, I., L.Y. Hsu, M. Saini, A. Weiss, and B. Seddon. 2014. J Immunol 193:2873-2880.
6. Marshall, D., C. Sinclair, S. Tung, and B. Seddon. 2014. J Immunol 193:5525-5533.
7. Sinclair, C., Bains, I., Yates, A. and B. Seddon 2013. PNAS. 110 (31), E2905-E2914
8. Sinclair, C., Saini, M., van der Loeff, I.S., Sakaguchi, S., and Seddon, B. 2011. Sci Signal 4, ra77.

Defining T cell correlates of protection in people who resist SARS-CoV-2 infection

We identified an association between T cells targeting the essential highly conserved replication-transcription proteins of SARS-CoV-2 (e.g., polymerase and helicase) and protection from a detectable infection (Abortive infection; Swadling et al Nature 2022), we are now characterising this population of T cells to identify qualities and specificities that best correlate with protection. With Prof. Maini and Prof. Barnes (Uni of Oxford) we are testing designs for a pan-coronavirus vaccines based on this work.

Rational Design of cross-protective T cell vaccines

We are particularly interested in understanding ‘what determines the ability of a T cell to cross-recognise different viral variants or even different viruses’ and how vaccines can be rationally designed to induce the most cross-protective immunity. We are studying viral sequence evolution (Lucy van Dorp, UCL Genetics) and TCR characteristics (Dr Andreas Mayer, ULC) at cross-reactive epitopes to allow prioritisation of epitopes for inclusion in T cell vaccines.  

Bioinformatic Delineation of the TCR signature of HBV control

We are identifying protective TCR sequences from the site of infection, the liver, for use in next generation TCR gene therapy for hepatitis-B virus and to probe the biological link between specificity and function. We are also investigating T cell adaptation to the liver environment.

• Swadling et al. Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2 (2022) Nature. DOI: 10.1038/s41586-021-04186-8.
• Cankat et al. In search of a pan-coronavirus vaccine: next-generation vaccine design and immune mechanisms Cell Mol Immunol. 2024 Feb;21(2):103-118.
• Diniz et al. T cell control of SARS-CoV-2:When, Which and Where? (2023) Semin Immunol. doi: 10.1016/j.smim.2023.101828
• Swadling et al. Human Liver Memory CD8+ T Cells Use Autophagy for Tissue Residence. (2020) Cell Rep. DOI: 10.1016/j.celrep.2019.12.050

Emerging Virus Preparedness: Use of Gene Therapy Vectors

The current COVID-19 pandemic highlights importance of preparedness against emerging infectious diseases. While it is difficult to predict what pathogens will cause future pandemics, influenza viruses remain major suspects with high potential to cause pandemics. Furthermore, there are several regionally emerging viruses prioritised in the World Health Organisation (WHO) R&D Blueprint [1], including viruses like Zika virus (ZIKV) which in 2016 was declared a Public Health Emergency of International Concern. Many such viruses are currently the cause of tropical diseases with the potential to spread to temperate regions due to climate change.

Here I propose two possible PhD projects with the theme of emerging virus preparedness, both in collaboration with The Medicines and Healthcare products Regulatory Agency, Science, Research and Innovation (MHRA, SRI).

Universal immunoprophylaxis against influenza viruses by gene-delivered nanobodies (in collaboration with Dr Simon Hufton, Biotherapeutics and Advanced Therapies, MHRA)

We have been developing alpaca-derived, cross-subtype neutralizing single domain antibodies (nanobodies) against influenza and their delivery using gene therapy vectors [2]. This gene-mediated immunoprophylaxis approach may allow us to protect the high-risk population with poor vaccine response (e.g. immunocompromised patients, elderly etc) from a wide range of influenza strains including those new to humans with high pandemic potential. Further development includes broadening target strains, ‘humanisation’ of the nanobody constructs and optimization of nanobody effector function.

The student will study biochemistry and structural biology of nanobody-pathogen interaction, immunology focusing on nanobodyhost immune system interaction and gene therapy technology.

Development of pseudotypes of viruses with global epidemic potential (in collaboration with Dr Giada Mattiuzzo, Vaccines, MHRA)

The Emerging Virus Group at NIBSC has been contributing to a rapid response to emergencies caused by enveloped viruses by developing standards and assays for diagnostics and serology. These activities heavily rely on pseudotype virus (PV) technology based on gene therapy vector systems [3] which enables us to study dangerous viruses more safely and outside special containment like BSL3/4. While it has been relatively easy to make PVs for viruses that bud at the cell surface, e.g. Ebola virus, MERS [4] and SARS CoV-2 coronaviruses, we recognise our shortcomings in making PVs for viruses that bud intracellularly, e.g. flaviviruses (dengue, zika etc).

This project will explore and compare current and new PV systems in order to increase our capability in PV making and assay development for a wider range of viruses including those yet unknown.

1. https://www.who.int/activities/prioritizing-diseases-for-research-and-development-inemergency-contexts
2. https://www.frontiersin.org/articles/10.3389/fimmu.2020.00627/full
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118154/?report=classic
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759245/

Chance and necessity in T cell fate decisions

This project aims to understand the rules governing T cell fate decisions. We can track the concordance of fate decisions of clonally-related cells using their hypervariable antigen receptors as natural barcodes. Combining machine learning and single-cell data, we aim to infer differentiation landscapes and how T cell receptor signalling biases fate.

Predicting antibody function from sequence

This project aims to understand the rules governing the generation of anti-viral antibodies (HIV and SARS-CoV-2). In collaboration with Laura McCoy (I&I) we investigate the role of B cell dysfunction and repertoire dynamics during immunisation/infection to decipher what makes particular epitopes better recognised by antibodies and what controls the diversity of responding B cells.

1. Contrastive learning of T cell receptor representations
   Y Nagano, A Pyo, M Milighetti, J Henderson, J Shawe-Taylor, B Chain*, A Tiffeau-Mayer*
   Cell Systems (2025
2. Tissue determinants of the human T cell receptor repertoire 
   S Sureshchandra, J Henderson, E Levendosky, S Bhattacharyya, JM Kastenschmidt, AM Sorn, M Tabassum Mitul, A Benchorin, K Batucal, A Daugherty, SJH Murphy, C Thakur, D Trask, G Ahuja, A Moisan, A Tiffeau-Mayer**, N Saligrama**, LE Wagar**
   bioRxiv preprint (2024)

Examples of possible projects in the lab include:

1. Regulation of B cell germinal centre reactions by antigen retention on follicular dendritic cells
2. Identification of novel mechanisms controlling IgE B cell responses in allergy
3. Mapping of pathways promoting the pathogenesis and transformation of B cell lymphomas

1. Martínez-Riaño, A., Wang, S., Boeing, S., Minoughan, S., Casal, A., Spillane, K. M., Ludewig, B. & Tolar, P. (2023) Long-term retention of antigens in germinal centers is controlled by the spatial organization of the follicular dendritic cell network. Nat. Immunol. 24, 1281-1294.
2. Chen, Q., Menon, R. P., Masino, L., Tolar, P.* & Rosenthal, P. B. (2023) Structural basis for Fc receptor recognition of immunoglobulin M. Nat. Struct. Mol. Biol. 30, 1033-1039. 
3. Newman, R. and Tolar, P. (2021) Chronic calcium signaling in IgE+ B cells limits plasma cell differentiation and survival. Immunity 54, 2756-2771.e10.
4. Spillane, K. M., Tolar, P. (2017) B cell antigen extraction is regulated by the physical properties of antigen presenting cells. J. Cell Biol. 216, 217-230.
5. Nowosad, C. R., Spillane, K. M., and Tolar, P. (2016) Germinal center B cells recognize antigen through a specialized immune synapse architecture. Nat Immunol 17, 870-77.
6. Natkanski, E., Lee, W.-Y., Mistry, B., Casal, A., Molloy, J.E., and Tolar, P. (2013) B cells use mechanical energy to discriminate antigen affinities. Science 340, 1587-1590.

1. Circadian control of HBV vaccine responses

Define how time of day influences vaccine-induced T-cell immunity. Using advanced flow cytometry, you will process mouse tissues to characterise the magnitude and quality of vaccine-elicited responses.

2. Visualising the circadian clock during HBV infection

Apply cutting-edge RNAscope imaging to map circadian gene expression in immune cells and HBV-infected hepatocytes, uncovering spatial interactions between host clock machinery and viral replication.

3. Identification of novel antivirals via circadian modulator screening

Evaluate small-molecule circadian modulators for their ability to restrict HBV replication, using both in vitro infection models in CL3 and in vivo mouse models, with the aim of developing new host-targeted antiviral strategies.

You will gain expertise in:

• Multi-colour flow cytometry and immune assays
• In vitro and in vivo circadian and infection models
• Advanced imaging, RNAscope, and spatial transcriptomics
• Analysis of patient-derived clinical samples

Key Questions We Aim to Answer

• How does the circadian clock regulate T-cell responses to HBV?
• Can manipulating circadian rhythms improve vaccine efficacy?
• Do circadian disruptions drive chronic HBV infection and liver disease progression?

Why Join Us?

You will join a vibrant, multidisciplinary team with strong collaborative links, working alongside local PIs and leading researchers in Oxford, Cambridge, and across the globe. This is more than a PhD - it is a unique opportunity to help shape the future of viral immunology, make discoveries with direct translational potential, and contribute to worldwide efforts against one of the deadliest viruses.

1. Borrmann H, Ulkar G, Kliszczak AE, Ismed D ... Zhuang X, McKeating JA. Molecular components of the circadian clock regulate HIV-1 replication. iScience. 2023 May 29;26(7):107007. doi: 10.1016/j.isci.2023.107007.
2. Zhuang X, Edgar RS, McKeating JA. The role of circadian clock pathways in viral replication. Semin Immunopathol. 2022 Mar;44(2):175-182. doi: 10.1007/s00281-021-00908-2. Epub 2022 Feb 22.
3. Zhuang X, Tsukuda S, Wrensch F, Wing PAC, et al. The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells. iScience. 2021 Oct 22;24(10):103144. doi: 10.1016/j.isci.2021.103144.
4. Zhuang X, Forde D, Tsukuda S, D'Arienzo V, et al. Circadian control of hepatitis B virus replication. Nat Commun. 2021 Mar 12;12(1):1658. doi: 10.1038/s41467-021-21821-0.
5. Wing PA, Davenne T, Wettengel J, Lai AG, Zhuang X, et al. A dual role for SAMHD1 in regulating HBV cccDNA and RT-dependent particle genesis. Life Sci Alliance. 2019 Mar 27;2(2):e201900355. doi: 10.26508/lsa.201900355.