Dr Michael Morgan

Dr Michael Morgan
Dr Michael Morgan
Dr Michael Morgan

Lecturer

Accepting PhDs

About

Biography

The vision for my lab is the life course engineering of the immune system to promote healthy ageing. I work at the intersection of computational and experimental biology to identify molecular and cellular mechanisms that are affected by ageing and genetics, including the regulation of cell state, response to stimulation and cell-cell communication. My lab develops computational algorithms that are applied to single-cell 'omics data which allowing a broader impact of our research.

I have trained in a mixture of wet-lab experimentation techniques and computational biology in Leeds, Oxford and Cambridge before starting my lab here in Aberdeen.

 

Qualifications

  • BSc Hons Medical Genetics 
    2010 - University of Huddersfield 
  • PhD Pharmacogenetics 
    2013 - University of Leeds 

Memberships and Affiliations

Internal Memberships

Institute of Medical Sciences Equality, Diversity and Inclusion committee

Aberdeen Computational Biology Forum - founder & organiser

British Society of Immunology - Aberdeen Immunology Group committee

IMS ECR Seminar Series -  founder & organiser

External Memberships

Genetics Society

British Society for Immunology

International Society for Computational Biology

Latest Publications

View My Publications

Research

Research Overview

My lab studies how ageing and genetics regulate immune cell states and cell-cell interactions, and how this impacts on immune-mediated diseases, notably autoimmunity. By developing state of the art computational algorithms, we model variation in cell states and cell-cell interactions using single cell 'omics data modalities. This involves combining graph theory and statistical models to identify which cell types or interactions are perturbed by ageing and genetics. The impact of our research is broadened by the computational algorithms that we develop, and their application through collaborations with research groups that study cancer and immunology both nationally and internationally.

Potential PhD student candidates should contact me to discuss supervision opportunities.

 

Research Areas

Accepting PhDs

I am currently accepting PhDs in Biomedical Sciences.


Please get in touch if you would like to discuss your research ideas further.

Email Me

Biomedical Sciences

Accepting PhDs

Research Specialisms

  • Bioinformatics
  • Human Genetics
  • Genomics
  • Immunology

Our research specialisms are based on the Higher Education Classification of Subjects (HECoS) which is HESA open data, published under the Creative Commons Attribution 4.0 International licence.

Current Research

Single-cell omic profiling has revealed a bewildering diversity of cell types and states defined at the mRNA and protein levels. We are now in the position to scale up these experiments to profile biological systems across large cohorts of volunteers and patients to understand how these cell states are affected by our genetic make-up and the environments that we live in. Moreover, by profiling complex compositions of cells using dissociated single-cell RNA-sequencing and spatial transcriptomic/proteomic approaches we can resolve how interactions between cells are regulated at the genetic level, how this manifests as cell-to-cell variability, and how this predisposes people to immune-mediated diseases.

Computational research

In my previous appointment I developed a computational algorithm, called Milo, to identify perturbed cell states from single-cell experiments (Dann et al. Nature Biotech 2022). Milo uses a blend of graph theory (nearest-neighbour graphs) and statistical modelling (generalized linear models) to identify which cell states are enriched or depleted in an experiment. My lab continues to develop this framework to incorporate mixed effect models and employ graph-theory to improve the computational speed. Such advancements open the door to statistical genetic analyses of single cell data. My lab uses these computational advances to solve biomedical problems from basic research to disease - which broadens the impact of our research.

For further reading see Dann et al., Nature Biotech 2022 and Kluzer et al., bioRxiv 2023

Experimental research

I have recently developed an in vitro system to co-culture and stimulate peripheral immune system cells as a  model of immune response and T cell:antigen presenting cell interactions. The motivation is to use this experimental system to probe how ageing and genetic variation shapes the way that immune cells communicate with each other to shape and direct proper immune responses. Using statistical genetics, we can then identify which genetic variants alter immune cell activation and cell-to-cell communication, and how this predisposes to a range of immune-related diseases, such as autoimmunity and cancer.

Past Research

My research to-date has spanned quantitative genetics, immunology and computational biology to understand the genetic and genomic regulation of cell-to-cell variability in protein and mRNA levels, altered cell fate decision-making in the ageing thymus, and the immune-related changes in blood of COVID19 patients at single-cell resolution. In tandem, I have developed the computational algorithms to integrate single-cell 'omic data and identify altered cell state abundance in single-cell experiments.

A word cloud encompasses the research focus of the Morgan lab.
Generated using https://shiny.rcg.sfu.ca/u/rdmorin/scholar_googler3/

Select publications

Kluzer et al., bioRxiv 2023, Milo2.0 unlocks population genetic analyses of cell state abundance using a count-based mixed model

Dann et al., Nature Biotechnology 2022, Milo: differential abundance testing on single-cell data using k-NN graphs

Stephenson et al., Nature Medicine 2021, Single-cell multiomics analysis of the immune response in COVID-19.

Baran-Gale et al., eLife 2020, Ageing compromises mouse thymus function and remodels epithelial cell differentiation

Morgan et al., PLoS Genetics 2020, Quantitative genetic analysis deciphers the impact of cis and trans regulation on cell-to-cell variability in protein expression levels

Eling, Morgan & Marioni, Nature Reviews Genetics 2019, Challenges in measuring and understanding biological noise

Morgan & Marioni, Genome Biology 2018, CpG island composition differences are a source of gene expression noise indicative of promoter responsiveness

Collaborations

Collaborations

Georg Holländer - University of Basel & Oxford University - Progeny-progenitor relationships in the thymic epithelium

Doug Winton - Cancer Research UK-Cambridge Institute, University of Cambridge - Genetic and genomic regulation of intestinal stem cell dynamics

Alejandra Bruna - Institute of Cancer Research, London - Evolution of chemotherapeutic resistance in neuroblastoma

Tim Halim - Cancer Research UK-Cambridge Institute, University of Cambridge - Single-cell profiling of innate-like lymphoid cells in pancreatic cancer

Maike de la Roche - Cancer Research UK-Cambridge Institute, University of Cambridge - The role of Gli1 and hedgehog signalling in thymocyte development

Patrick Cao - Institute of Medical Sciences, University of Aberdeen - Developing Lecto-seq for combined single-cell profling of glycan-lectin interactions and transcriptomes

Funding and Grants

Royal Society Ageing and autoimmunity - the Ying and Yang of CTLA-4 and T cell function: (December 2023 - November 2024) - £69,557.25

Friends of ANCHOR Pushing the right buttons: a physiologically relevant, controllable, system for T cell activation in cancer research: (August 2023 - July 2024) - £11,827.01

Lab startup funds - £10,000

PhD studentship - £78,000

Publications

Page 1 of 2 Results 1 to 10 of 20

  • Origin and segregation of the human germline

    Castillo-Venzor, A., Penfold, C. A., Morgan, M. D., Tang, W. W., Kobayashi, T., Wong, F. C., Bergmann, S., Slatery, E., Boroviak, T. E., Marioni, J. C., Surani, M. A.
    Life Science Alliance, vol. 6, no. 8, e202201706
    Contributions to Journals: Articles
  • Sequential enhancer state remodelling defines human germline competence and specification

    Tang, W. W. C., Castillo-Venzor, A., Gruhn, W. H., Kobayashi, T., Penfold, C. A., Morgan, M. D., Sun, D., Irie, N., Surani, M. A.
    Nature Cell Biology, vol. 24, no. 4, pp. 448-460
    Contributions to Journals: Articles
  • Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19

    Wang, J., Kotagiri, P., Lyons, P. A., Al-Lamki, R. S., Mescia, F., Bergamaschi, L., Turner, L., Morgan, M. D., Calero-Nieto, F. J., Bach, K., Mende, N., Wilson, N. K., Watts, E. R., Maxwell, P. H., Chinnery, P. F., Kingston, N., Papadia, S., Stirrups, K. E., Walker, N., Gupta, R. K., Menon, D. K., Allinson, K., Aitken, S. J., Toshner, M., Weekes, M. P., Nathan, J. A., Walmsley, S. R., Ouwehand, W. H., Kasanicki, M., Göttgens, B., Marioni, J. C., Smith, K. G. C., Pober, J. S., Bradley, J. R., Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) Covid BioResource Collaboration
    iScience, vol. 25, no. 3, pp. 103971
    Contributions to Journals: Articles
  • PBMC isolation

    Morgan, M.
    protocols.io.
    Other Contributions: Other Contributions
  • The impact of hypoxia on B cells in COVID-19

    Kotagiri, P., Mescia, F., Hanson, A. L., Turner, L., Bergamaschi, L., Peñalver, A., Richoz, N., Moore, S. D., Ortmann, B. M., Dunmore, B. J., Morgan, M. D., Tuong, Z. K., Göttgens, B., Toshner, M., Hess, C., Maxwell, P. H., Clatworthy, M. R., Nathan, J. A., Bradley, J. R., Lyons, P. A., Burrows, N., Smith, K. G. C., Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) Covid BioResource Collaboration
    EBioMedicine, vol. 77, 103878
    Contributions to Journals: Articles
  • Differential abundance testing on single-cell data using k-nearest neighbor graphs

    Dann, E., Henderson, N. C., Teichmann, S. A., Morgan, M. D., Marioni, J. C.
    Nature Biotechnology, vol. 40, no. 2, pp. 245-253
    Contributions to Journals: Articles
  • Cells of the human intestinal tract mapped across space and time

    Elmentaite, R., Kumasaka, N., Roberts, K., Fleming, A., Dann, E., King, H. W., Kleshchevnikov, V., Dabrowska, M., Pritchard, S., Bolt, L., Vieira, S. F., Mamanova, L., Huang, N., Perrone, F., Goh Kai'En, I., Lisgo, S. N., Katan, M., Leonard, S., Oliver, T. R. W., Hook, C. E., Nayak, K., Campos, L. S., Domínguez Conde, C., Stephenson, E., Engelbert, J., Botting, R. A., Polanski, K., van Dongen, S., Patel, M., Morgan, M. D., Marioni, J. C., Bayraktar, O. A., Meyer, K. B., He, X., Barker, R. A., Uhlig, H. H., Mahbubani, K. T., Saeb-Parsy, K., Zilbauer, M., Clatworthy, M. R., Haniffa, M., James, K. R., Teichmann, S. A.
    Nature, vol. 597, no. 7875, pp. 250-255
    Contributions to Journals: Articles
  • Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease

    Bergamaschi, L., Mescia, F., Turner, L., Hanson, A. L., Kotagiri, P., Dunmore, B. J., Ruffieux, H., Sa, A. D., Huhn, O., Morgan, M. D., Gerber, P. P., Wills, M. R., Baker, S., Calero-Nieto, F. J., Doffinger, R., Dougan, G., Elmer, A., Goodfellow, I. G., Gupta, R. K., Hosmillo, M., Hunter, K., Kingston, N., Lehner, P. J., Matheson, N. J., Nicholson, J. K., Petrunkina, A. M., Richardson, S., Saunders, C., Thaventhiran, J. E., Toonen, E. J., Weekes, M. P., Göttgens, B., Toshner, M., Hess, C., Bradley, J. R., Lyons, P. A., Smith, K. G., Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) Covid BioResource Collaboration
    Immunity, vol. 54, no. 6, pp. 1257-1275.e8
    Contributions to Journals: Articles
  • Single-cell multi-omics analysis of the immune response in COVID-19

    Stephenson, E., Reynolds, G., Botting, R. A., Calero-Nieto, F. J., Morgan, M. D., Tuong, Z. K., Bach, K., Sungnak, W., Worlock, K. B., Yoshida, M., Kumasaka, N., Kania, K., Engelbert, J., Olabi, B., Spegarova, J. S., Mende, N., Jardine, L., Gardner, L. C. S., Goh, I., Horsfall, D., McGrath, J., Webb, S., Mather, M. W., Lindeboom, R. G. H., Dann, E., Huang, N., Polanski, K., Prigmore, E., Gothe, F., Scott, J., Payne, R. P., Baker, K. F., Hanrath, A. T., Loeff, I. C. D. S. v. d., Barr, A. S., Sanchez-Gonzalez, A., Bergamaschi, L., Mescia, F., Barnes, J. L., Kilich, E., Wilton, A. d., Saigal, A., Saleh, A., Janes, S. M., Smith, C. M., Gopee, N., Wilson, C., Coupland, P., Coxhead, J. M., Kiselev, V. Y., Dongen, S. v., Bacardit, J., King, H. W., Rostron, A. J., Simpson, A. J., Hambleton, S., Laurenti, E., Lyons, P. A., Meyer, K. B., Nikolić, M. Z., Duncan, C. J. A., Smith, K. G. C., Teichmann, S. A., Clatworthy, M. R., Marioni, J. C., Göttgens, B., Haniffa, M.
    Nature Medicine, vol. 27, pp. 904-916
    Contributions to Journals: Articles
  • Ageing compromises mouse thymus function and remodels epithelial cell differentiation

    Baran-Gale, J., Morgan, M. D., Maio, S., Dhalla, F., Calvo-Asensio, I., Deadman, M. E., Handel, A. E., Maynard, A., Chen, S., Green, F., Sit, R. V., Neff, N. F., Darmanis, S., Tan, W., May, A. P., Marioni, J. C., Ponting, C. P., Holländer, G. A.
    eLife
    Contributions to Journals: Articles
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