Events

Heterogeneity of viral disease across strains and host cell types

Event date: 
23 January 2019 - 3:30pm
Location: 
Lowy Level 4 Seminar Space
Booking deadline: 

Special Seminar - Speaker: Dr Fabio Zanini

Bio: I obtained an MSc in Physics with Prof. Frank Schreiberand Prof. Marina Scarpa at the University of Tuebingen , the Institut Laue Langevin , and the University of Trento with a thesis on light and neutron scattering on concentrated protein solutions [1] . During my PhD in Bioinformatics, obtained in 2015 at theMax Planck Institute for Developmental Biology with Prof. Richard Neher, I identified the genomic changes governing the evolution of the human immunodeficiency virus (HIV) in untreated patients [2–5] . Since 2016 I am a postdoc with Prof.Stephen Quake at Stanford University. Here I elucidated the the effect offlavivirus infection in thousands of single cells in cell lines [6] and in the blood of severe dengue patients, built models to improve disease prognosis, and identified antiviral monoclonal antibodies [7] . My current work focuses on decoding the heterogeneity of viruses and human disease using single cell transcriptomics, statistical models, and microfluidics. I am particularly interested in (i) linking viral and host cell heterogeneity to disease outcome in infected tissues and tumors and (ii) discovering therapeutic antibodies against viruses and oncoviruses. 

Abstract: 36 million people are living with human immunodeficiency virus (HIV) and an increasing number of them develop resistance to antiretroviral drugs. 400 million people are infected annually by dengue virus and can develop severe symptoms, yet prognosis and treatment are largely ineffective. For both diseases, a major obstacle towards better diagnostics and therapeutics is the heterogeneity of viral strains as well as the host cell populations infected in vivo. I have explored the genomic changes in untreated HIV infections via whole-genome deep sequencing and elucidated the basic rules governing HIV evolution inside human patients. I have then analyzed the gene expression of thousands of single immune blood cells from severe dengue patients and identified (i) the cell populations associating with virus and (ii) multiple biomarkers associated with progression to severe symptoms. The combination of high-throughput sequencing, single cell resolution, and bioinformatics can greatly expand our knowledge, diagnostics, and therapeutics for heterogeneous viral disease.

References:

1. Heinen M, Zanini F, Roosen-Runge F, Fedunová D. Viscosity and diffusion: crowding and

salt effects in protein solutions. Soft Matter. pubs.rsc.org; 2012; Available:

http://pubs.rsc.org/en/content/articlehtml/2012/sm/c1sm06242e

2. Zanini F, Brodin J, Thebo L, Lanz C, Bratt G, Albert J, et al. Population genomics of

intrapatient HIV-1 evolution. Elife. 2015;4. doi: 10.7554/eLife.11282

3. Zanini F, Puller V, Brodin J, Albert J, Neher RA. In vivo mutation rates and the landscape of

fitness costs of HIV-1. Virus Evolution. 2017;3. doi: 10.1093/ve/vex003

4. Brodin J, Zanini F, Thebo L, Lanz C, Bratt G, Neher RA, et al. Establishment and stability of

the latent HIV-1 DNA reservoir. Elife. 2016;5. doi: 10.7554/eLife.18889

5. Zanini F, Neher RA. Quantifying Selection against Synonymous Mutations in HIV-1 env

Evolution. J Virol. 2013;87: 11843–11850

6. Zanini F, Pu S-Y, Bekerman E, Einav S, Quake SR. Single-cell transcriptional dynamics of

flavivirus infection. Elife. 2018;7. doi: 10.7554/eLife.32942

7. Zanini F, Robinson ML, Croote D, Sahoo MK, Sanz AM, Ortiz-Lasso E, et al. Virus-inclusive

single-cell RNA sequencing reveals the molecular signature of progression to severe

dengue. Proc Natl Acad Sci U S A. 2018; doi: 10.1073/pnas.1813819115

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20 March 2019

Room 305, Level 3, Samuels Building, UNSW Upper Campus, Kensington

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