Anatomy, Physiology and Human Biology

Lions Eye Institute Student Research Projects 2015

Below is a sample of research projects available at the Lions Eye Institute (LEI).

Students undertaking LEI projects will receive co-supervision by a member of the School of Anatomy, Physiology and Human Biology.

Contact Silvana Gaudieri <silvana.gaudieri@uwa.edu.au> to discuss supervision and enrolment details.

Experimental Immunology Lions Eye Institute Experimental Immunology

Project 1

Project type — Suitable for Honours, Masters or PhD studies

Supervisor(s) Laboratory Email
Professor Mariapia Degli-Esposti Experimental Immunology mariapia@lei.org.au (Primary)
Dr Matthew Wikstrom Experimental Immunology MatthewWikstrom@lei.org.au
Co-supervisor)
 

Details of project — Viruses and Autoimmune Disease in the Eye

The phenomenon of immune privilege is believed to protect the eye from autoimmunity by sequestering auto-antigens and preventing local immune activation. However, experimental models of autoimmune uveitis clearly demonstrate that autoimmunity can be readily induced by systemic immunisation. In our recent experiments, we have demonstrated that infection with cytomegalovirus, a common human pathogen, is also able to induce autoimmune uveitis. Our next step is to learn more about how a common viral infection is able to induce autoimmunity in the eye.

 This project will take advantage of our experience with mouse cytomegalovirus and ocular immunology. Laboratory work will entail engineering recombinant mouse cytomegalovirus, characterising the pathogenesis of infection in mice, and live imaging of the retina to assess the development of autoimmunity.

Project references

  1. Zinkernagel, M. S., Petitjean, C., Wikstrom, M. E. and Degli-Esposti, M. A. (2012) Kinetics of ocular and systemic antigen-specific T-cell responses elicited during murine cytomegalovirus retinitis. Immunol Cell Biol, 90: 330-336.
  2. Forrester, J. V., Steptoe, R. J., Klaska, I. P., Martin-Granados, C., Dua, H. S., Degli-Esposti, M. A. and Wikstrom, M. E. (2013) Cell-based therapies for ocular inflammation. Prog Retin Eye Res, 35: 82-101.

Research interests

Professor Mariapia Degli-Esposti’s group central focus is to determine the key cellular and molecular interactions that occur in response to viral infection. In recent years this research has provided important contributions to understanding how the immune system responds to infection and how, in turn, pathogens manipulate host immunity to improve their chances of survival. Mouse cytomegalovirus (MCMV) is used as a model virus infection, due to its similarity in structure and biology with the human cytomegalovirus (HCMV).

Research theme

  • Infectious diseases/autoimmunity

Scientific discipline

  • Immunology

Keywords

Eye, virus, ocular immune response, autoimmune uveitis

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Project 2

Project type — Suitable for Honours

Supervisor(s) Laboratory Email
Professor Mariapia Degli-Esposti Experimental Immunology mariapia@lei.org.au (Primary)
Dr Matthew Wikstrom Experimental Immunology MatthewWikstrom@lei.org.au
Co-supervisor)
 

Details of project — Tracking the fate of an inhaled virus

Cytomegalovirus is a common human pathogen. Infection is normally asymptomatic though the virus can produce severe disease in immunocompromised individuals such as the newborn and patients undergoing bone marrow or organ transplantation. Murine cytomegalovirus has been used widely to study acute and chronic infection, however most experimental models employ unnatural routes of infection.

This project will take advantage of our experience with mouse cytomegalovirus and immunology to track the fate of fluorescent cytomegalovirus after inhalation. Laboratory work will entail characterising the pathogenesis of infection in mice, fluorescent imaging of infected organs, and flow cytometry.

Project references

  1. Andrews, D. M., M. J. Estcourt, C. E. Andoniou, M. E. Wikstrom, A. Khong, V. Voigt, P. Fleming, H. Tabarias, G. R. Hill, R. G. van der Most, A. A. Scalzo, M. J. Smyth and M. A. DegliEsposti (2010). Innate immunity defines the capacity of antiviral T cells to limit persistent infection. J Exp Med, 207(6): 1333-43.
  2. Zinkernagel, M. S., Petitjean, C., Wikstrom, M. E. and Degli-Esposti, M. A. (2012) Kinetics of ocular and systemic antigen-specific T-cell responses elicited during murine cytomegalovirus retinitis. Immunol Cell Biol, 90: 330-336.

Research interests

Professor Mariapia Degli-Esposti’s group central focus is to determine the key cellular and molecular interactions that occur in response to viral infection. In recent years this research has provided important contributions to understanding how the immune system responds to infection and how, in turn, pathogens manipulate host immunity to improve their chances of survival. Mouse cytomegalovirus (MCMV) is used as a model virus infection, due to its similarity in structure and biology with the human cytomegalovirus (HCMV).

Research theme

  • Infectious diseases

Scientific discipline

  • Immunology

Keywords

Eye, virus, mucosal immune response, pathogenesis

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Project 3

Project type — Suitable for Honours

Supervisor(s) Laboratory Email
 Dr Jerome Coudert Experimental Immunology jerome@lei.org.au (Primary)



 

Details of project — Natural Killer cell and cytomegalovirus interaction

This research project will examine how NK cell functions are regulated and will seek to gain a more precise understanding of the cytomegalovirus immune evasion strategies.

Human cytomegalovirus (HCMV) is a common pathogen typically encountered in childhood. Although primary infection is readily controlled in healthy individuals, immune response fails to eliminate the virus resulting in latent infection that persists for life. In immunocompromised patients, HCMV is responsible for severe diseases that may lead to life threatening conditions. Mouse cytomegalovirus (MCMV) is very similar in structure and biology to HCMV, hence, MCMV is a widely utilised experimental model. MCMV studies evidenced that Natural Killer (NK) cells play a critical during acute infection, also, individuals with defective NK cells exhibit extreme sensitivity to viruses.

During hundreds of millennia of co-evolution with its host species, cytomegaloviruses have developed numerous immuno-regulatory genes that play an immune evasion role. Several immunoevasins have been identified in both HCMV and MCMV, however, the mechanisms that regulate NK cell antiviral response remain to be precisely understood.

This research project will involve animal experimentation in mouse infected with MCMV. The major techniques will be in vitro NK cell assays, flow cytometry and will also involve molecular biology techniques.

Project references

  1. R. Berry, N. Ng, P.M. Saunders, J.P. Vivian, J. Lin, F.A. Deuss, A.J. Corbett, C.A. Forbes, J. Widjaja, L.C. Sullivan, A.D. McAlister, M.A. Perugini, M.J. Call, A.A. Scalzo, M. Degli-Esposti, J.D. Coudert, T. Beddoe, A.G. Brooks and J. Rossjohn. Targeting of natural killer cell receptor family by viral immunoevasin. Nature immunology. 2013;14(7): 699-705.
  2. C.A. Forbes, A.A. Scalzo, M.A. Degli-Esposti and J.D. Coudert. Ly49C-Dependent Control of MCMV Infection by NK cells is Cis-regulated by MHC Class I  Molecules. PLOS pathogens. 2014; 10(5): 1-16.

Research interests

Professor Mariapia Degli-Esposti’s group central focus is to determine the key cellular and molecular interactions that occur in response to viral infection. In recent years this research has provided important contributions to understanding how the immune system responds to infection and how, in turn, pathogens manipulate host immunity to improve their chances of survival. Mouse cytomegalovirus (MCMV) is used as a model virus infection, due to its similarity in structure and biology with the human cytomegalovirus (HCMV).

Research theme

  • Infectious diseases/immune evasion

Scientific discipline

  • Immunology

Keywords

Virus, immune response, NK Cells

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Project 4

Project type — Suitable for Honours, Masters or PhD studies

Supervisor(s) Laboratory Email
Professor John Forrester Experimental Immunology JohnForrester@lei.org.au
Professor Mariapia Degli-Esposti
Experimental Immunology mariapia@lei.org.au
Dr Valentina Voigt
Experimental Immunology vvoigt@lei.org.au
 

Details of project — CMV induced infectious uveitis

Uveitis (intraocular inflammation) is the fourth commonest cause of blindness world-wide. Clinically many cases are caused by infection, but in around 50% of cases no cause can be identified. Cytomegalovirus (CMV) is a known infectious agent for uveitis, but it is unclear whether the disease is caused by viral damage or by an exaggerated immune response against the virus. This project aims to investigate the immune response against murine cytomegalovirus(MCMV) using state-of-the art in vivo imaging techniques correlated with morphological studies (immunohistochemistry) and flow cytometry analysis to follow changes in host T, B and NK cell cell responses during the development of MCMV uveitis. MCMV provides a unique model of viral infection, due to its similarity in structure and biology with human CMV and the fact that MCMV is a natural pathogen of mice.

This project complements a parallel project using a recombinant strain of MCMV.

Project references

  1. Dang, Z., Kuffova, L., Liu, L., and Forrester, J.V. (2014). Soluble antigen traffics rapidly and selectively from the corneal surface to the eye draining lymph node and activates T cells when codelivered with CpG oligonucleotides. J Leukoc Biol 95, 431-440.
  1. Forrester, J.V., Klaska, I.P., Yu, T., and Kuffova, L. (2013). Uveitis in mouse and man. Int Rev Immunol 32, 76-96.

Research interests

Professor Forrester is working on pathogenetic mechanisms regulating autoimmunity and infection and has many years experience in models of uveitis and techniques for evaluating ocular immune phenomena.

Research theme

  • Infectious diseases/autoimmunity

Scientific discipline

  • Immunology

Keywords

Eye, virus, ocular immune response, autoimmune uveitis

 

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Outback Medicine Lions Eye Institute Logo

Project 5

Project type — Suitable for Honours

 
Supervisor(s) Laboratory Email
A/Prof Angus Turner Outback Vision Angus.turner@gmail.com



 

Details of project — Monitoring and evaluating teleophthalmology in Western Australia

Aim: an observational study, by consecutive case series, of real-time teleconsultations performed for eye patients in Western Australia.
Hypothesis: teleophthalmology is a safe, accurate and cost-effective means of providing access to specialist services for a subset of patients in rural and remote Western Australia.

Brief description: Teleophthalmology is the delivery of specialist ophthalmic services to patients in a different geographical location, using telecommunications technology.

In 2011 a teleophthalmology service commenced in Western Australia. This real-time service operates between a general ophthalmologist based at the Lions Eye Institute, and several general practitioners, optometrists and hospitals in rural and remote Western Australia.

At present, there is a paucity of data on the efficacy of real-time teleophthalmology services, especially relating to patient satisfaction, barriers to utilisation, clinical efficacy and costeffectiveness. This project proposes to address this gap in evidence by evaluating the teleophthalmology service in Western Australia, identify its utility and limitations, and provide recommendations for future. It is envisaged that the results will be significant and worthy of publication in a medical journal, given the novel nature of the project, potential benefit to patients and relevance to eye care programs in Australia and overseas.

Methodological Approach

  • Study design: prospective, consecutive case series
  • Objective: to monitor the use and evaluate the effectiveness of teleophthalmology for patients requiring eye care in Western Australia over a defined period of time.
  • Literature review: published and appropriate unpublished literature on teleophthalmology
  • Data collection: develop and validate metrics for evaluating episodes of care via teleconsultation; design and maintain database of teleconsultation episodes of care.
  • Statistical analysis: dedicated data technical specialist input.
  • Report: write up results for thesis presentation with secondary aim of journal publication.

Role of the student

Perform the following roles under supervision and with support: literature review, data collection, provide input on statistical analysis and first author of the final report.

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Project 6

Project type — Suitable for Honours

 
Supervisor(s) Laboratory Email
A/Prof Angus Turner Outback Vision Angus.turner@gmail.com



 

Details of project — Monitoring and evaluating a culturally-appropriate teleophthalmology service in Western Australia

Aim: an observational study, by consecutive case series, of real-time teleconsultations performed for eye patients in Western Australia.
Hypothesis: teleophthalmology is a safe, accurate and cost-effective means of providing access to specialist services for a subset of patients in rural and remote Western Australia.

Brief description: Teleophthalmology is the delivery of specialist ophthalmic services to patients in a different geographical location, using telecommunications technology. In 2011 a teleophthalmology service commenced in Western Australia. This real-time service operates between a general ophthalmologist based at the Lions Eye Institute, and several general practitioners, optometrists and hospitals in rural and remote Western Australia.

At present, there is a paucity of data on the efficacy of real-time teleophthalmology services, especially relating to patient satisfaction, barriers to utilisation, clinical efficacy and cost effectiveness.

This project proposes to address this gap in evidence by evaluating the teleophthalmology service in Western Australia, identify its utility and limitations, and provide recommendations for future.
It is envisaged that the results will be significant and worthy of publication in a medical journal, given the novel nature of the project, potential benefit to patients and relevance to eye care programs in Australia and overseas. While telemedicine has been generally well received by patients and providers, Indigenous Australians’ perceptions of telemedicine are unknown.
As many patients managed by video-consultation will be Indigenous, an assessment of whether telemedicine provides a culturally-appropriate model of providing healthcare may also be included. Hence, the findings of this project may have broader relevance to any program that includes telemedicine as a means of healthcare delivery to this population.

Methodological Approach
  • Study design: prospective, consecutive case series
  • Objective: to monitor the use and evaluate the effectiveness of teleophthalmology for patients requiring eye care in Western Australia over a defined period of time.
  • Literature review: published and appropriate unpublished literature on teleophthalmology
  • Data collection: develop and validate metrics for evaluating episodes of care via teleconsultation; design and maintain database of teleconsultation episodes of care.
  • Statistical analysis: dedicated data technical specialist input.
  • Report: write up results for thesis presentation with secondary aim of journal publication.

Role of the student

Perform the following roles under supervision and with support: literature review, data collection, provide input on statistical analysis and first author of the final report.

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Ocular Tissue Engineering Lions Eye Institute Logo

Project 7

Project type — Suitable for Honours

 
Supervisor(s) Laboratory Email
Dr Samuel McLenachan (primary)
Ocular Tissue Engineering
smclenachan@lei.org.au
Asoc Prof Fred Chen (Co-supervisor)
Ocular Tissue Engineering fredchen@lei.org.au
 

Details of project — Induction of Pluripotency in Limbal Stem Cells

The human corneoscleral limbus contains multipotent stem cells that can be isolated and cultured for clinical applications, such as the treatment of limbal stem cell deficiency.
Studies in rodents have shown that limbal stem cells can be cultured as floating neurospheres that can be further dedifferentiated to pluripotency without the use of traditional reprogramming techniques that employ transcription factor delivery.

Limbal neurospheres (LiNS) express three (SOX2, KLF4 and C-MYC) of the four transcription factors identified as being sufficient for reprogramming cells to pluripotency, lacking only Oct4, the master pluripotency gene. Culture of LiNS in embryonic stem cell conditioned media is sufficient to induce Oct4 expression and an induced pluripotent stem cell phenotype in rodent LiNS, however the induction of pluripotency from primary human LiNS has not yet been reported.
In this project the effects of microRNAs on pluripotent gene expression and induction of pluripotency will be examined in human LiNS cultures.

Project references

  1. Balasubramanian, S., N. Babai, et al. (2009). "Non cell-autonomous reprogramming of adult ocular progenitors: generation of pluripotent stem cells without exogenous transcription factors." Stem Cells 27 (12): 3053-3062.
  2. McLenachan, S., D. Zhang, et al. (2014). Stem Cells of the Human Corneoscleral Niche. Regenerative Biology of the Eye, Springer 215-239.
  3. McLenachan, S., D. Zhang, et al. (2013). "mRNA transfection of mouse and human neural stem cell cultures." PLoS One 8(12): e83596.

Research Interests

The Ocular Tissue Engineering Laboratory was established in 2011 with the aim of developing stem cell therapies for retinal diseases such as Age-related Macular Degeneration (AMD). Our research interests include the culture and differentiation of adult stem cells, induction of pluripotent and retinal cell fate by cellular reprogramming and extracellular matrix production using macromolecular crowding. With a focus on clinical translation, we have combined these research themes to develop an autologous retinal pigment epithelial patch for the treatment of AMD.

Research Theme

  • Cellular Programming

Scientific Discipline

  • Stem Cell Biology

Keywords

  • pluripotency, induced pluripotent stem cells, limbal stem cells
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