Margaret J Lange
University of Missouri-Columbia, MO·Microbiology & Immunology
HIV remains a major global health problem, and one of its proteins is unusually central to how the virus works. The capsid protein, abbreviated CA, forms the shell that encloses the viral genome, and it participates in many steps of infection: assembling new virus particles, maturation, copying the viral RNA into DNA by reverse transcription, traveling to the cell nucleus by grabbing onto host proteins, entering the nucleus, inserting into host DNA, and hiding the virus from immune detection.
- Fields
Microbiology & Immunology
Biochemistry
Biophysics
- Topics
capsid
CA protein
RNA aptamers
- Grants
- 2 known grants, through Mar 2031
What they work on
- Identify new RNA aptamers, short structured nucleic acids selected for tight binding, that recognize additional HIV-1 capsid assembly forms, building toward a panel covering the lattice, hexamer and pentamer states.
- Develop aptamer-mediated affinity purification that isolates one capsid assembly state at a time, paired with crosslinking mass spectrometry, to identify host proteins associated with each state.
- Elucidate the molecular basis of aptamer-capsid binding by mapping which epitopes, or surface patches, of the capsid protein each aptamer targets.
- Build aptamer-based biosensors that change conformation on binding, to detect specific capsid structural forms in defined cell compartments, including capsid core entry into the nucleus before 2-LTR circles form.
- Select and characterize aptamers that bind capsid in the presence of host factors or of lenacapavir, a capsid-targeting antiviral, to probe how drug and host binding alter capsid structure.
- Determine the biological significance of aptamer-capsid interactions in cells, testing proposed interactions between specific capsid structural forms and host factors to inform new therapeutic targets.
More about the research
CA manages all these jobs by folding into different shapes and assembly arrangements at different stages. Studying it is hard: CA is genetically fragile, so mutating it often just breaks the virus, and there have been no tools that recognize one structural form of CA and not another. Both projects in this lab build such tools out of RNA.
Why it matters
HIV capsid is the target of a new class of antiviral drugs, and tools that distinguish its structural forms could reveal fresh, accessible sites on the protein for drug design and clarify which forms matter at which stage of infection. The aptamer biosensors could also support more sensitive detection methods, including cost-effective tests for capsid forms or viral drug resistance, and the approach could extend to capsids of other viruses of public health importance.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Yi Xiao
North Carolina State University, NC·Chemistry
Develop NA-SELEX, an aptamer selection method that uses DNA-cutting nucleases so neither target nor library sits on a solid support, to find aptamers that bind tightly and stay bound under body-like conditions.
Jeannette Tenthorey
University of California-San Francisco, CA·Microbiology & Immunology·Early-career
Build stable, high-complexity HIV-1 libraries containing all possible single missense mutations across the capsid, using new tools that overcome long-standing barriers to producing saturating mutant viral libraries.
Masahiro Yamashita
Columbia University, NY·Microbiology & Immunology
Develop a high-throughput neutralization assay in which each HIV envelope (Env) variant in a lentiviral system carries a unique DNA barcode, allowing simultaneous tracking of hundreds of variants against ten broadly neutralizing antibodies targeting five gp120 sites.
The school
University of Missouri-Columbia: 21 labs on PI Pages, $509M a year on research, 260 research doctorates a year.
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