Biomolecular imaging at the University of Auckland

The following blog post has been provided by Dr Grus Grey:

Our group is focused on applying spatially resolved imaging technologies, such as MALDI imaging mass spectrometry and fluorescence microscopy, to investigate the molecular basis of ocular diseases and advance our efforts to treat these diseases.

As a core technology, we use MALDI imaging to detect endogenous molecules, such as glutathione in the lens.

The ability to study its transport and its regeneration pathways enables us to better understand how the age-related deficiency of this primary lens antioxidant may lead to cataracts in specific lens regions.

The use of MALDI imaging mass spectrometry for biomolecular investigation: application to the ocular lens and cataract research

Both human lenses of different ages (Fig A), and aging models of bovine lenses have been used to demonstrate age-related changes to glutathione and related molecules.

Furthermore, we trace the uptake and metabolism pathways of other nutrients, such as glucose, and drug molecules by introducing stable isotopic labels (SIL) to ex vivo tissue. The use of SIL in this system harnesses the power of MALDI FT-ICR imaging to capture a large quantity of data while maintaining very high m/z resolution. This allows differentiation between endogenous molecules and exogenous SIL molecules, which only contain a small mass shift, thus enabling specific detection as well as comparative quantification in our studies.

Figure B displays our work in tracking the presence of endogenous glucose and uptake of SIL glucose into the lens. It is known that in the absence of a blood supply, the ocular lens operates a microcirculation of ions and water that aids optical performance and transparency. However, the precise role that the lens microcirculation plays in nutrient transport and metabolic waste removal requires further work.

With a goal of bettering the development of ocular drug formulations and preventing off target effects, we investigate the uptake, transport and metabolism of nutrients and pharmacological compounds.

The spatial information produced by MALDI imaging, with complimentary protein labelling using fluorescence microscopy, can provide knowledge of distinct intrinsic mechanisms which may be exploited for treatment purposes.

Lastly, with strong collaborative links we also apply MALDI imaging to study other major human diseases such as cancer and neurodegeneration to discover novel disease biomarkers, therapeutic targets, and therapeutic agents.

The MALDI imaging equipment is part of a wider Mass Spectrometry Hub located at the University of Auckland. For further information on biomolecular imaging using MALDI, please contact Dr Gus Grey.