Evolutionary Dynamics of Infectious Diseases
Fabio Luciani
Research Interests
Viral evolution and host pathogen interactions
I work on mathematical models of viral evolution. Please
contact me or see my
publications.
Hepatitis C virus and its evolutionary dynamics
I am interested in modeling of Hepatitis C virus dynamics. HCV is a rapidly mutating virus with fascinating dynamics. It can evolve very quickly within a host and escape immune responses. My interest is in the population dynamics and epidemiology of HCV infections and in understanding the role of host heterogeneity in driving viral evolution. For instance, I am working on the role of MHC frequency distribution and its effect in determining the probability of escape mutants.
Recently we also started a new project using Next Generation Sequencing (NGS) applied to HCV viral dynamics. This technique allows the detection of rare species of the virus and therefore allows a detailed quantification of viral evolution. We are using NGS to also detect escape mutants that avoid immune responses causing chronic infections.
Please, contact me for more information and for few computer programs that I developed with my
collaborators.
T cell dynamics and Antigen presentation
I am interested in the mechanisms behind antigen processing and presentation in the context of MHC class I response. To date, I am working on a project in collaboration with Dr Weisan Chen (Ludwig Institute Melbourne)on the dynamical evolution of immunodominance in T cell responses against influenza virus in mice. Students can contact me for
available projects.
Molecular epidemiology
A great application of mathematical models of infectious diseases is the study of transmission dynamics of complex pathogens, such as bacteria. Given their complex genomes, it is often hard to study directly changes in the DNA sequence of these organisms. Therefore scientists have come up with few typing scheme. With these, it is possible to sequence only few pieces of the genome and use this as fingerprint of bacterial strains. I use these schemes to study the transmission dynamics of bacterial pathogens, such as Mycobacterium tuberculosis, Neisseria meningitidis, streptococcus and others.
I also work in collaboration with statisticians here at UNSW (
Dr Scott Sisson) and theoretical epidemiologists at the Imperial college of London (Dr Fraser ad Dr Hanage). We are applying Approximate Bayesian Computations (ABC) methods to estimate the transmission dynamics and relative fitness of drug resistant strains of mycobacterium tuberculosis.
Statistical analyses of hepatitis C virus in injecting drug users
Since 2008, I am involved in the epidemiological and statistical analyses of a large cohort of HCV infected subjects in NSW prisons, , the
Hepatitis C
Incidence and
Transmission
Study (HITS). Currently, I am responsible for the statistical analyses of a large epidemiological, virological and immunological dataset on early evolution of the virus in these subjects, see my publications.
Media
Occasions where my research has been picked up by the media:
•
Fears for zookeepers after TB spreads to chimps, Sydney Morning Herald, November 2011
•
New hope for hep C vaccine, UNSW Media, News & Events, September 2011
•
Scientists warn of drug-resistant TB, Sydney Morning Herald, August 2009
•
New TB strains a spreading danger, The Canberra Times, August 2009
•
New drug-resistant TB strains could become widespread says new study, UNSW Science News, August 2009
Publications
Bull RA*,
Luciani F*, McElroy K, Gaudieri S, Pham ST, Chopra A, Cameron B, Maher L, Dore GJ, White PA, Lloyd AR. Sequential bottlenecks drive viral evolution in early acute hepatitis C virus infection.
PLoS Pathogens 2011 Sep;7(9):e1002243. Epub 2011 Sep 1.
* Equally contributed
Alizon S.,
Luciani F., Regoes R. Epidemiological and clinical consequences of within-host evolution.
Trends in Microbiology (In Press). IF 6.894 EJR=A*.
Review on the state of the art of quantitative analysis of withib host evolutionary dynamics in human infectious diseases.
Teutsch S,
Luciani F, McCredie L., Teutsch S, Luciani F, Scheuer N, McCredie L, Hosseiny P, Rawlinson W, Kaldor J, Dore GJ, Dolan K, Ffrench R, Lloyd A, Haber P, Levy M. Incidence of primary hepatitis C infection and risk factors for transmission in an Australian prisoner cohort.
BMC Public Health. 2010 Oct 22;10(1):633. IF 2.223 EJR=B.
It shows significant factors associated to incidence of HCV in prisons of New Wouth Wales. The analysis involves multivariate statistical analysis as well as standard univariate analysis.
McLean A.
Luciani F, Tanaka M. Trade-offs in resource allocation in the intracellular life-cycle of hepatitis C virus.
The Journal Theoretical Biology. 2010, 267 (2010), pp. 565-572.
IF 2.5, EJR=A*. It uses mathematical modelling to show a trade-off in HCV viral replication using intracellular dynamics in infected cells.
Luciani F, Alizon S. The evolutionary dynamics of a rapidly mutating virus
within and between hosts: the case of hepatitis C virus.
PLoS Comput. Biol. 2009 Nov 5(11): e1000565. Epub 2009 Nov 13.
Journal Impact Factor: 5.895, ISI ranking: 1/29 in Mathematical and Computational biology journals; 5/65 in Biochemical Research Methods journals].
Luciani F, Sisson SA, Jiang H, Francis AR, Tanaka MM.
The epidemiological fitness cost of drug resistance in Mycobacterium tuberculosis.
Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14711-5. Epub 2009 Aug 13.
Journal impact Factor: 9.38 (Five-Years Impact Factor 10.228), second best Eigenfactor (1.7) across all ISI journals. ISI ranking: 3/42 in Multidisciplinary sciences journals].
Tang C, Reyes JF,
Luciani F, Francis AR, Tanaka MM. SpolTools: online
utilities for analyzing spoligotypes of the Mycobacterium tuberculosis complex.
Bioinformatics. 2008 Oct 15; 24(20):2414-5. Epub 2008 Aug 18. Journal Impact Factor: 5.039, ISI ranking: 2/29 in Mathematical and Computational Biology journals; 10/65 Biochemical Research Methods journals. Cited 3.
Mishto M,
Luciani F, Holzhütter
HG, Bellavista
E, Santoro
A, Textoris-Taube
K, Franceschi C, Kloetzel
PM, Zaikin A. Proteasome modelling algorithm to predict
in vitro kinetics of 20S proteasome degradation.
J Mol Biol. 2008 Apr 11; 377(5):1607-17. Journal Impact Factor: 4.52, ISI ranking 74/275 in Biochemistry and Molecular Biology journals. Cited 3.
Pomati F, Orlandi C, Clerici M,
Luciani F, Zuccato E. Effects and
interactions in an environmentally relevant mixture of pharmaceuticals.
Toxicol Sci. 2008 Mar; 102(1):129-37. Epub 2007 Nov 28. Journal Impact Factor: 4.4. ISI ranking 5/75 in Toxicology journals. Cited 12.
Luciani F, Francis AR, Tanaka MM. Interpreting genotype cluster sizes of
Mycobacterium tuberculosis isolates typed with IS6110 and spoligotyping.
Infection, Genetics and Evolution. 2008 Mar;8(2):182-90. Epub 2008 Feb 1. Journal Impact Factor: 2.792. ISI ranking: 22/51 in Infectious Diseases journals. Cited 5.
Tanaka M, Francis A,
Luciani F, Sisson S. Using approximate Bayesian
computation to estimate tuberculosis transmission parameters from genotype data.
Genetics 2006 Jul; 173(3):1511-20. Journal Impact Factor: 4.289. ISI ranking: 32/138 in Heredity and Genetics journals. Cited 10.
Luciani F, Keºmir C, Mishto M, Or-Guil M, De Boer RJ. A mathematical
model of protein degradation by the proteasome.
Biophys J. 2005 Apr;88(4):2422-32. Epub 2005 Jan 21.
Luciani F., Turchetti G., Valensin S., Bonafe M., Franceschi C.
A stochastic model for the clonal expansion of cytotoxic T lymphocytes.
Ricciardi L.M. and Sato S. (eds.) Special Issue on BIOCOMP 2002, p. 439-453.
SCMJ, Vol. 58, No. 2, 2003. JAMS, Osaka.
Luciani F., Valensin S., Vescovini R., Sansoni P., Fagnoni F., Franceschi C., Bonafe M., Turchetti G. A stochastic model for the CD8+ T cell dynamics in human Immunosenescence: implications for Survival and Longevity.
Journal of Theoretical Biology, 2001 Dec 21; 213(4):587-97.
Luciani F, Turchetti G., Franceschi C., Valensin S. A mathematical model for the Immunosenescence.
Rivista di Biologia/Biology Forum May-Aug;94(2):305-18, 2001.
Collaborations
I collaborate with other theoreticians and also experimental scientists:
Future Students
Prospective students are encouraged to check my
research interests and then
contact me directly with some idea of a research area you wish to work in.
Applications for
Australian Postgraduate Awards (APA) and other scholarships close in October. Citizens and permanent residents of Australia and NZ are eligible to apply
Below you can find some ideas:
Project n.1 Immunology
Title: The control of immunodominance in T cell responses against influenza infections in mice.
This project focuses on modeling the T cell response against influenza infection and on the estimate of parameters that best fit experimental data. The project is in collaboration with Dr Weisan Chen and Dr Ken Pang from the Ludwig Institute for Cancer Research. They provide me with experimental observation of T cell responses in an influenza mouse model.
Suitable for PhD, Masters or Honours
Project n.2 Immuno-Virology
Title: Immuno-virological predictors of HCV clearance.
This project is based on recent advanced technologies (pyrosequencing or more commonly known as deep sequencing) that allow the detection of the complex quasi-species distribution characterizing HCV infections rare viral strains circulating in the infected host. The project involves the bioinformatics analysis of recent data we obtained from our HITS cohort of HCV infected individuals from NSW prisons. We aim at detecting the why some viral strains lead to chronic infections and other strains are cleared by the immune system.
Suitable for PhD, Masters or Honours
Grants and Awards
Fellowships
| NHMRC Postdoctoral Training Fellowship - Biomedical Sciences | 2008-2012 |
| UNSW Vice Chancellor Postdoctoral Fellowship | 2008-2010 |
Award Australian Academy of Sciences – travelling fellowship
Visiting Scientist at the CNRS (French National Centre for Scientific Research). Topic: “The evolutionary epidemiology of rapidly mutating viruses: Are infection traits controlled by the host or by the virus?”. | 2010 |
Award
Winner of the national competition “Premio Lando Caiani” for the best Masters Thesis in the field of Theoretical Physics in the year 2000.
Award from the SISSA, International School for Advanced Studies Trieste, Italy.
Scholarship 2001 – 2002
Institute: Max Planck Institute for the Physics of Complex Systems Dresden, Germany.
Topic: Mathematical models of antigen presentation and of the dynamics of T cell clones
Scholarship 2000 – 2001
Institute: Institute of Experimental Pathology, University of Bologna, Italy
Topics: Mathematical models for the dynamics of the immune system during ageing
Competitive grants:
• Chief investigator in
NHMRC Partnership Project – APP1016351 – Prevention and treatment of viral hepatitis amongst prisoners
• Two competitive grants (category I) from the Australian Centre for Hepatitis and HIV Research (2009-2010, $230,000) on predictors of HCV infection outcomes
• Chief investigator in a partnership grant between University of New South Wales and NSW Health Department (2010-2012) on predictors of HCV infection outcomes in NSW corrective services
• UNSW Early career researcher fund (2008)
Teaching and Workshops
Coordinator of the module Medical Science of the SCIF 1121 (from 2010)
Workshops on application of statistics in Medical Science for undergraduate and postgraduate students
Seminars on mathematical models and Bioinformatics in studying infectious diseases
Conferences
Invited speaker at the Hepatology & Luminal Workshop to be held on 16 & 17 May, 2011 at the Sebel Harbourside, Kiama, New South Wales as annual meeting of the Gastroenterology Society of Australia: “Use of high-throughput sequence technologies to quantify viral evolution in HCV”.
Oral presentation to the EASL 2011 (27March - 2 April 2011) Berlin, Germany. Talk: Evolutionary dynamics of hepatitis C virus during very early infections: virological and immunological insights.
http://www2.kenes.com/liver-congress/Pages/Home.aspx
Oral presentation at the MEEGID 2010, 10th International Conference on Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases. November 3-5, 2010, Amsterdam, the Netherlands. Evolutionary dynamics of hepatitis C virus: deep sequencing analysis of very early infections.
http://www.meegidconference.com/
Oral presentation at the 17th International Meeting on Hepatitis C Virus and Related Viruses, Yokohama, Japan, September 10-14, 2010. Evolutionary dynamics of hepatitis C virus: deep sequencing analysis of very early infections.
http://www.hcv2010.jp/index.html
Invited speaker at the International Workshop on "Evolution in Health and Disease", September 22-26, Instituto Gulbenkian de Ciencia in Lisbon (2008). Title: Bayesian statistical methods applied to molecular epidemiology of infectious diseases.
Invited speaker at the Sixth ECMTB, European Conference on Mathematical and Theoretical Biology ECMTB05, Dresden Germany. Title: The role of antigen presentation in shaping T cell responses against intracellular pathogens.
http://www.ecmtb05.org/
Invited speaker at the International Conference on Computational and Mathematical Population Dynamics. Title: A mathematical model for proteasome degradation: channel configuration regulates the fragment length distribution. Trento, Italy, 21-25 June 2004.