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Mang Ching Lai

Postgraduate Student

Research Summary

My research project is focused on dissecting the molecular mechanisms underlying haplotype-specific regulation of gene expression at the microtubule associated protein tau (MAPT) locus. The effects of MAPT haplotype-specific variations on several gene regulatory processes, including alternative splicing, co-transcriptional splicing and microRNA regulation of gene expression, will be investigated in this project.

Herpes simplex virus type 1 (HSV-1) amplicon-based infectious bacterial artificial chromosome (iBAC) vectors expressing the complete MAPT locus (~143 kb) (iBAC-MAPT) will be used in our studies for maintaining the physiological expression level of the locus and for retaining genomic features including promoter regulation and alternative splicing. BAC modification techniques will be used for modifying haplotype-specific sequences on the MAPT gene. HSV-1 has a high transgene capacity and will allow for efficient infectious delivery of the iBAC-MAPT vectors for expression in different cell culture models.

Two major haplotypes, H1 and H2, have been described at the MAPT locus. H1 haplotype was identified in several genome wide association studies to strongly associate with increased risks for Parkinson's disease, progressive supranuclear palsy and corticobasal degeneration. Understanding the genetic mechanisms at the MAPT locus is thus important in providing insights into how common variations in the MAPT gene could lead to variable risks for developing certain neurodegenerative diseases.

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I completed a BSc in Biochemistry course at Essex University where I worked on characterising the biochemical properties of several rhodopsin mutants that cause autosomal dominant retinitis pigmentosa under the supervision of Dr Philip Reeves. I then undertook an MSc in Clinical Neuroscience degree at the Institute of Neurology, University College London. I worked on investigating the molecular mechanisms underlying C9orf72 mutation in neurodegeneration under the supervision of Dr Adrian Isaacs.

My main interests are understanding the molecular mechanisms of neurodegenerative diseases and developing treatments. I joined the Wade-Martins group in 2012, funded by the Alzheimer's Society, to investigate on the molecular mechanisms underlying haplotype-specific regulation of expression at the microtubule associated protein tau locus. The project is supervised by Dr Richard Wade-Martins and Dr Tara Caffrey.