Keratoconus is a progressive, non-inflammatory corneal dystrophy affecting 1 in 2000 of the younger working age population. Various treatment options exist including conservative methods (soft and rigid contact lenses) and surgical interventions (intra stromal corneal rings). However, profound astigmatism and corneal scarring ultimately requires corneal transplantation for visual rehabilitation in a proportion of individuals. Recently, photodynamic collagen cross-linking using ultraviolet A (UVA) irradiation combined with the photosensitiser riboflavin has been proposed as a less invasive treatment (and less costly) option for the management of keratoconus. However, the long-term risks and benefits of collagen cross-linking are poorly understood.

The aim of this study is to investigate biochemical and physiological aspects of collagen cross-linking in human corneal tissue in vitro and in vivo.
 

• Ophthalmology
• Optometry
   

This project has a Band 2 fee. Details of different fee bands are available for UK/EU or International applicants. See: Fees.

The HIV pandemic is one of the greatest challenges facing healthcare providers across the globe today. Worldwide 33.2 million people were HIV positive at the end of 2007 with 2.5 million new cases reported that year. Highly active antiretroviral therapy (HAART), is the current treatment for HIV, however HAART does not cure HIV infection and also has several disadvantages including severe, unpleasant side effects as well as the emergence of resistance. Prevention of HIV transmission would therefore be a better approach and requires a vaccination or microbicide approach. Attempts to develop an HIV vaccine have so far been unsuccessful. New microbicides may therefore represent the best opportunity to prevent transmission of HIV, and thereby lessen the pandemic.

One source of such microbicides may be antimicrobial peptides. Dr Dobson’s group have previously developed a range of peptides based on a cationic sequence within apolipoprotein E and apolipoprotein B with broad antiviral activity, including activity against HIV, both blocking viral entry into cells and selectively disrupting the viral envelope. The peptides inhibit all strains of HIV tested, and herpesviruses. The peptides would be suitable for development as microbicides for topical application to prevent HIV transmission. This project will focus on the further development of these peptides as microbicides against HIV and HSV2.

Specifically the study will identify more potent peptides and features associated with potency whilst retaining biocompatibility. A small a library of peptides will be screened primarily against HSV2, and ultimately against HIV, benchmarking against existing candidate microbicides. Activity will be correlated with a range of structural properties of the peptides, assessed using state of the art biophysical techniques. Additionally, the impact of formulation in standard microbicidal gels will be assessed as will the influence of physiological fluids on activity.
 

• Kelly, B.A., Harrison, I., McKnight, A. & Dobson, C.B (2010). Anti-infective activity of apolipoprotein domain derived peptides in vitro: identification of novel antimicrobial peptides related to apolipoprotein B with anti-HIV activity. BMC Immunology, 11, 13.

• Kelly BA, Neil SJ, McKnight A, Santos JM, Sinnis P, Jack ER, Middleton DA, Dobson CB. (2007). Apolipoprotein E-derived antimicrobial peptide analogues with altered membrane affinity and increased potency and breadth of activity. FEBS Journal, 274, 4511-4525.

• Dobson CB, Sales SD, Hoggard P, Wozniak MA, Crutcher KA. (2006). The receptor-binding region of human apolipoprotein E has direct anti-infective activity. J Infec Dis, 193(3), 442-450.

• Dobson C.B., Wozniak M.A. and Itzhaki R.F. (2003). Do infectious agents play a role in dementia? Trends in Microbiology, 7: 312-317.
 

• Biochemistry
• Biomolecular Sciences
• Biotechnology
• Cell Biology
• Immunology
• Microbiology
• Pharmacology
• Structural Biology

This project has a Band 3 fee. Details of different fee bands are available for UK/EU or International applicants. See: Fees.

The ability of a contact lens to support a stable tear film during wear is one of the key requirements to achieving compatibility with the ocular environment. In turn, this is related to the surface properties of the lens material, and in particular its ‘wettability’. A lens with good wettability improves wearer comfort, vision, and reduces biofouling of its surface. Drop-outs from contact lens wear are a significant problem in the contact lens industry and discomfort has consistently been reported as the most common cause of discontinuation from lens wear. In vivo wettability can be assessed using a range of relatively crude tests which have been used for several decades. These include: tear film break up time, interferometric techniques, and various techniques based around specular reflection. These methods usually fail to adequately differentiate between different lens surfaces, even when very different lenses are evaluated. In order to try to overcome this problem, we have recently successfully developed a novel instrument (Novel On-eye Wettability Analyser: NOWA) which is able to measure in vivo contact angles and liquid spreading for contact lenses. The instrument has been able to quantitatively differentiate wettability between lenses and further, showed that subjective comfort was correlated to a novel parameter based on liquid spreading. Further research using the NOWA instrument will allow us: a) to refine the instrument, b) to investigate different contact lens wearing populations (e.g. dry eye subjects), c) to investigate the effect of deposition, d) to investigate the effect of different care regimes and e) to correlate the composition of the tear film with clinical wettability and comfort. Improvements in our understanding of the tear film and the potential to predict which contact lenses are likely to perform in a superior manner in-eye are expected to have clear benefits in terms of optometric clinical management, ultimately leading to improved patient care and a reduced drop-out from contact lens wear.

1. Haddad M, Maldonado-Codina C and Morgan PB. A novel technique for measuring contact angles in vivo. Invest Ophthalmol Vis Sci 2009; 50: E-abstract 5645
2. Read ML, Morgan PB and Maldonado-Codina C. Measurement errors related to contact angle analysis of hydrogel and silicone hydrogel contact lenses. J Biomed Mater Res B: Appl Biomater. 2009; 91B(2): 662-668.
3. Read ML, Morgan PB and Maldonado-Codina C. Dynamic contact angle analysis of silicone hydrogel contact lenses. J Biomater Appl March 10, 2010 [Epub ahead of print].
 

• Ophthalmology
• Optometry

This project has a Band 2 fee. Details of different fee bands are available for UK/EU or International applicants. See: Fees.

Glaucoma is a progressive optic neuropathy that affects many millions of people worldwide. Recent research has suggested that altered blood flow plays an important role in both the development and progression of glaucomatous optic neuropathy (GON). While there is no one standard method for monitoring blood flow within the retina, laser doppler flow and optical coherence tomography are commonly used in research laboratories and specialist clinical labs. These are quite technical procedures requiring expensive equipment and specialist knowledge and are also limited in the area that is probed in each scan.
Optical imaging is a technique for indirectly recording neural activity using light. Historically this technique has been employed to monitor the response properties of groups of cells in the neocortex of living animals. Our group in Manchester has been at the forefront of the development of this technique and its associated analysis software. Over the years we have built a number of imaging systems for recording activity from the brains of rodents and primates.
A recent intriguing report has suggested that optical imaging can be used to directly measure blood flow from the surface vessels of the human retina. This account presented data demonstrating flow impairment in the retinae of patients with a variety of eye disorders. Given current thinking that altered blood flow may significantly contribute to the development and be indicative of the prognosis of GON we have recently developed a new retinal imaging system based on a combination of an existing fundus camera and a high-resolution optical imaging camera. This project will make use of our new imaging system to monitor blood flow in retinae of diseased and normal retinae and correlate these findings with standard optometric measurements such as visual field maps.
 

• Neuroscience
• Ophthalmology
• Optometry
• Physiology
• Systems Neuroscience

This project has a Band 1 fee. Details of different fee bands are available for UK/EU or International applicants. See: Fees.

Sight loss is one of the commonest causes of disability in the UK, with around 2 million people affected. These patients with low vision use aids for a wide variety of daily tasks, and appear to derive great benefit from them. The most common low vision aids (LVAs) are optical hand and stand magnifiers. Telescopic aids are also used in hand-held form for distance orientation and navigation, and spectacle-mounted for intermediate tasks such as music, computers and TV.
A number of manufacturers worldwide produce optical magnifying devices, and strive to optimise the image quality: British Standards also set limits for aberration performance. The use of high quality devices inevitably adds to the cost of aids and to the technical difficulty of manufacture, and this could have consequences in developing countries where aids are in short supply. The precise role of “image quality” in the practical success of devices is by not clear. It has been suggested that this high resolution is “wasted” because the visual system of the low vision patient is not able to perceive much of this detail.
The most common complaint of patients using low vision aids is the poor field of view: in a survey, 83% of users identified this as a factor they would like to improve about their aid.
The appropriate field of view to carry out some tasks for which magnifiers are used (computing, music, TV) has not been assessed.
The aim of this project would be to identify the critical field sizes for the chosen tasks, and then determine whether small improvements in field of view created by sacrificing image quality could actually make performance better.
 

Hassan et al (2007) Vision Res 47 2115-2123
Leat and Rumney (1992) Applied Optics 31 3637-3645
Legge et al (2007) J. Vision vol 7 issue 2 Article 9
Watson et al (1997a) Optom Vis Sci 74 249-259
Watson et al (1997b) Optom Vis Sci 74 260-265
 

• Ophthalmology
• Optometry
   

This project has a Band 1 fee. Details of different fee bands are available for UK/EU or International applicants. See: Fees.

In the last decade, impressive progress has been achieved in the field of retinal imaging and the problem is now how to best use these images. Several commercial instruments have been developed that incorporate software to register/align large numbers of high quality images but these functions are relatively limited and usually offer little help for specific tasks. The development of efficient tools is thus required to reduce the time of processing and to use the full benefit of these imaging techniques. The project will focus on the development, implementation, and assessment of various registration, segmentation, and image enhancement techniques. Retinal images will be provided by the University of Manchester Vision Centre or the Manchester Royal Eye Hospital. The close proximity of eye care specialists will allow us to assess clinically the benefits of the investigated techniques. Candidates should have excellent mathematical and programming skills.
 

• Nonlinear registration for scanned retinal images: application to ocular polarimetry. V. Nourrit. J. M. Bueno, B. Vohnsen and P. Artal. Applied Optics 2008;47(29):5341–47.
• Blind deconvolution for high-resolution confocal scanning laser ophthalmoscopy. V. Nourrit, B. Vohnsen and P. Artal. Journal of Optics 2005; 10(7): 585-92

• Optometry

This project has a Band 1 fee. Details of different fee bands are available for UK/EU or International applicants. See: Fees.

Among the most surprising recent discoveries in sensory biology is that photoreception in the mammalian retina is not restricted to rods and cones. Instead, a small proportion of the retina’s projection neurons (so-called retinal ganglion cells, whose axons form the optic nerve) are intrinsically photosensitive. These ganglion cell photoreceptors absorb light using a specialist protein called melanopsin. They do not contribute directly to visual perception, but drive many sub-conscious visual responses including synchronisation of internal biological clocks to local time of day, improvements in mood and alertness, changes in gross physiology (e.g. body temperature and heart rate), and constriction of the pupil in our eye. Because these responses are not required for us to ‘see’ its easy to overlook their important contribution to human health and well-being. In fact, these new photoreceptors are unsung heroes in helping us avoid insomnia and depression and keeping us alert and productive.

I am happy to consider PhD candidates who are interested in studying this new and important sensory modality in either of the following ways:
1.) Determine how these ganglion cell photoreceptors support sub-conscious vision by recording neural activity in the brain of mice.
2.) Determine how melanopsin makes ganglion cells photoreceptive using molecular biology and cell culture techniques.
 

• Lall GS, Revell VL, Momiji M, al Enezi J, Altimus CM, Güler AD, Aguilar C, Cameron MA, Allender A, Hankins MW, Hattar S and Lucas RJ (2010). Distinct contributions of rod, cone and melanopsin photoreceptors to encoding irradiance. Neuron 66:417-28
• Güler AD, Ecker JL, Lall GS, Haq S, Altimus CM, Liao H-W, Barnard AR, Cahill H, Badea TC, Zhao H, Hankins MW, Berson DM, Lucas RJ, Yau K-W and Hattar S. (2008) Melanopsin cells are the principal conduits for rod–cone input to non-image-forming vision. Nature 453:102-105
• Bellingham J, Chaurasia SS, Melyan Z, Liu C, Cameron MA, Tarttelin EE, Iuvone PM, Hankins MW, Tossini G, Lucas RJ (2006) Evolution of melanopsin photoreceptors: Discovery and characterization of a new melanopsin gene in non-mammalian vertebrates PLoS Biology 4(8):e254
• Melyan Z, Tarttelin EE, Bellingham J, Lucas RJ, Hankins MW (2005). Addition of human melanopsin renders mammalian cells photoresponsive. Nature 433:741-5
• Lucas RJ, Hattar S, Takao M, Berson DM, Foster RG, Yau K-W (2003) Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice. Science 299:245-247. 

• Adaptive Organismal Biology
• Animal Biology
• Integrative Neurobiology and Behaviour
• Molecular and Cellular Neuroscience
• Neuroscience
• Opthalmology

This project has a Band 2 fee. Details of different fee bands are available for UK/EU or International applicants. See: Fees.