Understanding the role of mitochondrial haemoglobin - an in silico approach

• Main Author: Katyal, Gunjan
• Format: Thesis
• Language: English
• Published: 2022
• Subjects: Perutz; Thornton; Icefish
• Online Access: http://eprints.nottingham.ac.uk/68632/; https://eprints.nottingham.ac.uk/68632/1/Understanding%20The%20Role%20Of%20Mitochondria%20Hb%20V5_GunjanKatyal_09032022.pdf

About 60 years ago, Nobel Laureate, Max F. Perutz, who discovered the structure of the globular protein Haemoglobin (Hb), suggested that changes in the molecule were seen in neurodegenerative diseases and argued its role as a drug receptor. Neurodegeneration is more likely to be affected by a fundamental yet inevitable phenomenon of ageing. There has been sufficient evidence that changes in the powerhouse of the cell, mitochondria dysfunction, is one of the hallmarks of ageing and neurodegeneration. Yet we are still far off from deciphering direct links and pathways conclusively leading to it. The project was aimed to find that, if Hb is localised in the mitochondria, it must influence the proteins situated there. Hence to validate the theory the project entailed working on the unique and mysterious icefish that are the only vertebrate organisms without Hb and acted as a model to understand the differences observed in the presence/absence of this protein. In general protein-protein interactions (PPI) can influence many biological processes, metabolic pathways and, cell-to-cell interactions (Braun and Gingras, 2012). These interactions could be transient or permanent (Irene M A Nooren and Thornton, 2003), where transient interactions would form signalling pathways and permanent interactions will form a stable protein complex. New functionality of a characterised protein or a new protein can be predicted on the evidence of their interaction with well characterised proteins in the proteome. PPI data can be categorised into three types, -in vitro, which includes liquid chromatography (LC), gel-electrophoresis, western blots, coimmunoprecipitation, mass spectrophotometry (MS), X-ray crystallographic, NMR techniques, -in vivo, where the techniques are involved with the whole organism, -in silico, techniques involving, sequence and structural based approaches, chromosome proximity, phylogenetic tree, and proteins/gene expression data. The thesis entails in vitro and in silico approaches combined to decipher a Hb ...