©2019 by Michael Clarke-Whittet, all views expressed here are my own.

Michael Clarke-Whittet

I am a PhD student at the University of Surrey examining expression noise in biological systems at the post-transcriptional level. I aim to use RNA-binding systems to probe noise in gene expression and understand the factors that amplify and dampen it. When a protein is expressed in a cell the abundance is a signal. Any deviation from this abundance from cell-to-cell in the same population is termed noise, similar to how an analogue radio is tuned to receive a signal but other factors introduce noise into the total sound.

Protein abundance noise is an important factor in cellular decision making and survival, causing heterogeneity in a genetically identical population of cells. Understanding biological noise has important implications in drug efficacies against disease-causing cells like cancer and microbial infections, as well as biotechnological understanding of cellular expression. This research also aims to provide an experimental frame for investigating the relationship between noisy biological systems and quantum decoherence, the transition period where quantum objects resolve into classical physical objects such as electrons and protons.

 

During my master’s study at the University of Dundee I researched the interactions between cell-wall biosynthetic proteins in Group A Streptococcus. Using the principle of bacterial two-hybrid interactions I detected a pairwise interaction network between protein members of a polymer carbohydrate biosynthetic pathway.

I found that complexing was extensive in the enzyme group, and suggested that this indicates multiple labile complexed states that enables and control the reactions. I also found that the control of primary and secondary cell wall carbohydrate may co-interact via the streptococcal ExPortal and thus have a controlled export between the two types of carbohydrate.

 

My research in my honours year in Dundee focussed on constructing next-generation tagging vectors for use in Trypanosoma brucei, protozoa which cause serious diseases in sub-Saharan Africa. I constructed plasmid vectors to allow N-/C- tagging of proteins using a recently discovered fluorescent protein derived from a marine invertebrate which was suggested to be extraordinarily bright.

The purpose of this project was to enable quantification and microscopic localisation of the lowest 5% of expressed proteins, with the possibility of detecting just a handful of targets within a cell which is generally not feasible using more standard fluorescent tags. I also trialled the tagging system with CRISPR protein Cas9, to evaluate whether nucleic acid localisation can be achieved using the tagged Cas9 rather than by FISH.

 

In the final year of my bachelor’s degree, while on Erasmus exchange at the Hogeschool van Arnhem en Nijmegen (HAN), I took part in a collaboration project with Allison Woollard from the University of Oxford. This project focussed on understanding cancer-like disturbances in C. elegans seam cell regulation by RNAi knockdown and phenotype rescue. Also at HAN I investigated the biochemical basis of metastasis switching in melanoma via Activated Leukocyte Cellular Adhesion Molecule (ALCAM) remodelling.

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