Parasitology

Between 2005 and 2012 at the University of Edinburgh I worked on the Trypanosome parasite and its interaction with cattle hosts in the wild. 

Molecular Resistance to Cattle Sleeping sickness (Nagana) in cattle in East Africa

Tryp resistant and susceptible cattle were mined for candidate genes by genomic sweeps that a priori might be intrumental, at least in part, at explaining the Nagana suspectible and resistent cattle in East Africa. 

RNA was extracted in these cattle by me from organs linked to Nagana pathology, e.g. Spleen and liver cRNA interogated by Affymetrix biochips, also by me. From the data, gene pathways were mined to provide possible indicators of genetic and biochemical pathways underpinning disease.    

Publications: Tryp Sleeping sickness in WT cattle (Nagana)

I have published a number of seminal papers on this topic and also presented series of posters at conferences, both National and international.

See my academia profile:

(1) Laurence S Dawkins-Hall B.Sc (Hons), (Reg), CBiol, CSci, FIScT, FRSB, - University of Leicester

(2) Genetic and expression analysis of cattle identifies candidate genes in pathways responding to Trypanosoma congolense infection

(3) Genotype and expression analysis of two inbred mouse strains and two derived congenic strains suggest that most gene expression is trans regulated and sensitive to genetic background

Screening small compound libraries for binding efficacy to REL 1 using a Radio Ligand Assay

Based on in silico docking models, selective small compounds were predicted to bind to RNA Editing Ligase 1 (in Trypanosomes), a putative target gene for intervention therapy for Human African Trypanosomiasis (HAT). Actual compounds were  empirically screened using an established Radio Ligand assay and "hits" identified by this assay were  screened in vitro on live parasites for killing potential and efficacy graded using Michaelis Menten enzyme kinetics. 

Developing a Molecular Assay for screening small compound libraries linked to Tryp Killing

From 2008 to 2012 I looked at aspects of Human African Trypanosomiasis (HAT). 

In particular, I developed a FRET based assay for screening small compounds libraries with putative activity against the parasite target RNA Editing Ligase 1 (REL1) which hitherto had been postulated to be a potential target for killing parasites. The assay identified putative hits and these were tested against live Tryp parasites for killing efficacy in (Cat #3) culture using Alamar Blue. 

Publications linked to FRET Assay

Developing the FRET assay led to concomitant poster presentations at parasite conferences. After the final assay had been validated, data was written up and culminated in 2016 in a seminal paper in Nucleic Acid Research (NAR):

(1) Laurence S Dawkins-Hall B.Sc (Hons), (Reg), CBiol, CSci, FIScT, FRSB, - University of Leicester

(2) A novel high-throughput activity assay for the Trypanosoma brucei editosome enzyme REL1 and other RNA ligases

Publications resulting from Compound screening with a radio ligand assay

(1) Novel Naphthalene-Based Inhibitors of Trypanosoma brucei RNA Editing Ligase 1

Gene Expression: Elucidation of pathogenesis

Between 2005 and 2012, I engaged in wet bench work pertaining to genomic studies of gene expression underpinning  Bovine African sleeping sickness or "Nagana" in the field in Kenya, Africa and in laboratory based engineered mouse models. The purpose of these field based and in vivo studies was to elucidate snap shots of gene expression in different animal genotypes and attempt to identify genes seminal to the pathology of sleeping sickness in the wild.  

By way of example, and regarding temporal snap shots of gene expression in animal models:

  1. Field studies on candidate gene expression in the wild, putatively linked to African sleeping sickness.
  2. Conference posters on studies elucidating gene expression profiles in different pathogenic states of Nagana.
  3. A seminal paper in PNAS describing key genes in African Sleeping sickness in cattle.

Sleeping Sickness Resistance paper

A paper in which expression data sets linked to Tryp sleeping sickness resistance in the wild were generated by me using Affymetrix biochips to elucidate eQTLs with putative pathology linkage. This work was done by me during my time at the Roslyn Institute circa 2005-2008.

Sleeping Sickness Resistance paper

A paper in which expression data sets linked tosleeping sickness resistance in congenic models were generated by me using Affymetrix biochips, to elucidate eQTLs with putative pathology linkage. This work was done by me during my time at the Roslyn Institute circa 2005-2008.

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