Our Mission
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What do we do? |
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Transport, assembly and aggregation of neurotransmitters and proteins are finely tuned to ensure normal functioning of neurons. We aim to study monoamine transport and assembly, whose impairment is associated with a wide range of diseases ranging from depression to drug addiction. We are also investigating the transport and aggregation properties of cytoplasmic and membrane proteins which are implicated in pathologies such as Alzheimer’s disease and Creutzfeld-Jacob disease It is also our mission to continuously develop photonic tools for solving measurement problems such as these. |
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How do we do it? |
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Direct, non-invasive measurement of these properties in live, functioning neurons remains a technical challenge. Optical methods, while otherwise ideal, have faced two major hurdles a) many of these native biomolecules respond only in the ultraviolet (UV), and b) aggregation states of the molecules are not resolvable within the theoretical limits of optical resolution. We have demonstrated that multiphoton microscopy (MPM) can non-destructively harness UV fluorescence (Maiti et al. 1997a), and fluorescence correlation spectroscopy (FCS) can measure particle sizes down to sub-nanometer levels (Maiti et al., 1997b). However, lack of information about the optical and diffusional parameters of the relevant molecules presents the initial hurdle for exploiting these techniques. Our current efforts are geared towards solving this initial hurdle. |
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Current Efforts: |
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We have built an instrument that combines the power of these techniques for addressing our problems We have determined the multiphoton absorbance and photsostability properties of tryptophan and other chromophores, using techniques developed in-house. We have achieved an order of magnitude improvement in the sensitivity for detecting tryptophan (serotonin precursor) by utilizing novel excitation sources. We have employed FCS to measure diffusional transport (and therefore the hydrodynamic size) of protein aggregates and vesicles. We have investigated the aggregation of b -amyloid (implicated in Alzheimer’s disease) and the (putative) involvement of Apo-D in cholesterol transport (relevant to Niemann-Pick-C disease). We have applied FCS to investigate receptor oligomerization on membranes of chinese hamster ovary cells, and have developed a new method for analyzing FCS data in such complex systems. We have demonstrated an insertable confocal probe, which has the potential to perform many of these studies in vivo. |
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