Brien, James

Owned by UKY CCS RCD
Jun 09, 2024
2 min read

Research Activities

James Brien is an Assistant Professor of Microbiology, Immunology & Molecular Genetics, whose laboratory studies the immune mechanisms that underlie durable B cell responses and antibody-mediated protection against severe viral disease, and the control of viral variants. I am very excited to join UKY with great scientists, post-doctoral fellows and students. We have several projects including using our mRNA vaccine platform to understand how vaccine immunogenicity relates to correlates of protection against severe viral infection; the role of type I interferon in modulation of antigen-specific B cell responses to viral infection; and how viruses evolve away from different classes of antibody responses. We study a large panel of emerging pathogens that have a global impact including flaviviruses (dengue, Zika, and West Nile viruses), bunyaviruses (Rift valley fever, LaCrosse, hanta viruses), poxviruses (vaccinia, ectromelia, monkeypox viruses), coronaviruses (SARS-CoV-2, NL63, OC43, HKU, MERS-CoV).

Projects

mRNA vaccines trigger an innate and adaptive immune response, based upon lipid content and mRNA sequences. We are working on understanding how mRNA vaccines generate an antigen-specific immune response and provide protection.

Bone marrow transplantation is a critical therapeutic modality. The reconstitution of the innate and adaptive immune system is required for disease control but requires re-education. We are investigating how bone marrow transplantation affects vaccination and immune protection.

Emerging viral infections can cause devastating diseases as they spread through the human population. During infection host factors are critical in shaping viral populations ultimately influencing their evolution, potential to cause disease, and spread. We use mouse models of acute virus infection to evaluate how sites of replication, physical barriers and the pressure applied by host T and B cells affect viral genome sequence diversity.

Virus antigen diversity- As viral pathogens evolve functional diversity is a balance between virus replication and spread and escape from the immune response. We are mapping the polyclonal antibody response to viral antigens.

Computational Methods

All computational methods are well-developed and commonly used in the field.
This includes:

  • single cell sequencing-transcriptomics, ATAC-seq, BCR/TCR sequencing

  • bulk cell transcriptomic

  • viral genome sequence analysis

  • deep scanning mutagenesis

Software

jupiter notebook, conda
TCR/BCR analysis:airr b-cell T-cell immcantation immunorepertoire repseq
Single cell sequencing: 10x-genomics, 10xgenomics, alevin, bustools, cellranger, kallisto, rna-seq, single-cell, atac-seq
amplicon artic assembly
Virus sequencing: cat fastqc fastp kraken 2 bowtie 2 samtools iVAR picard mosdepth ivar variants BCFtools snpeff snpsift asciigenome bcftools, bedtools Quast Pangolin nextclade Cutadapt Spades unicycler blastn ABACAS plasmidID quast MultiQC
Sequence variation: dms_tools2, phydms,

Collaborators

UKY
Amelia K Pinto
Ilhem Messaoudi
Chris Radka
Qi Qiao

Non-UKY
Greg Ebel
Justin Richner
James Weger
Mariah Hassert
Daniela Weiskopf
Lark Coffey

Center for Computational Sciences