School of Life Sciences

I graduated with a BSc (Hons) in Biochemistry and Applied Molecular Biology from the University of Manchester Institute of Science and Technology (UMIST) before going on to complete a PhD at the University of Edinburgh investigating the DNA replication machinery of the human malarial parasite Plasmodium falciparum. Between 1996 and 1998, I worked at the University of Würzburg in Germany where I started to become interested in understanding stage-specific gene regulation in P. falciparum as well as a molecular investigation of parasite’s virulence factor PfEMP1. In 1998 I returned to the UK to the Weatherall Institute of Molecular Medicine, University of Oxford, where I worked with Prof. Newbold on the Malaria Genome Project and the antigenic switching and cytoadhesive properties of PfEMP1. Between 2003 and 2005 I was located at at the Liverpool School of Tropical Medicine before moving to the Institute for Science and Technology at Keele University on a Royal Society Relocation Fellowship. In 2006 I was appointed a Lecturer in the School of Medicine and became involved in the development and delivery of a new MBChB curriculum. I have since had the role of colead for year 1 (Challenges to Health) and am currently year 4 colead (Advanced Clinical Experience). In 2009 I received a BBSRC New Investigator Award and was promoted to Senior Lecturer. I am an ordinary member of council for the British Society of Parasitology, on the editorial board for Case Reports in Infectious Disease and am a member of University Senate.

I lead one of the six research groups within the Institute for Science and Technology in Medicine that study the biology of the human malarial parasite P. falciparum, its pathogenesis and transmission by the mosquito vector. My work is focussed on the biology of the malarial parasite – and in particular the intraerythrocytic stages on infection in the human host, the principle developmental stages responsible for the pathology of disease.

My research addresses the following areas;

• An investigation of the molecular mechanisms that direct the epigenetic and genetic control of gene expression during intraerythrocytic development
• The application of bioluminescence as a tool to study the action of antimalarial drugs
• An exploration of the action of novel classes of antimalarial drugs

Control of gene expression during intraerythroctyic development is controlled though a variety of molecular mechanisms operating at the epigenetic and genetic levels (Horrocks et al. 2009). Our research interests focus on how these operate to regulate the absolute and temporal programme of expression of house-keeping genes. We employ the use of cell culture, laboratory and bioinformatics techniques to help us better understand their interplay.

Reporter gene studies explore the effect of deletion of sequences that flank genes (Wu et al. 2011) and are combined with bioinformatics analyses to determine the effect of nuclear trans-acting factor against putative cis-acting factors.

We have also modelled the spatio-temporal organisation of the large transcriptional units in P. falciparum to better understand how large transcripts are arrayed over the relatively compact genome. This not only provides some interesting insights into the selective pressures on the parasite’s genome, but has also been extended to facilitate a comparative analysis of intergenic space organisation in other Apicomplexan parasites that are important for both human and veterinarian health. The nature of the sequences in these intergenic regions have also been explored – and show some interesting features of spatial organisation around key landmarks for gene expression.

More recently, we have been exploring the application of bioluminescence as a tool to monitor various aspects of antimalarial drug activity. Comparison against fluorescence assays reveal the two assays share similar profiles, however, bioluminescence may offer attractive opportunities in the development of rate-of-kill and lethal dose estimations.

There is an urgent demand to explore the potential of novel classes of drugs for their potential as new leads for antimalarial development. My laboratory collaborates with colleagues at Keele and Nottingham Trent University in an exploration of the structure activity relationship for synthetic monoindole alkaloids (Horrocks et al., 2012) and chemically modified glycosaminoglycans. The latter, are particularly attractive as their putative mode of action during the inhibition of erythrocyte invasion may be exploited to explore similar invasion blocking activity for a range of Apicomplexan parasites.‌

Our laboratory collaborates closely with other members of Keele University (Life Sciences and Chemistry), nationally with Nottingham Trent University and Charnwood Molecular Ltd and internationally with colleagues at the Universities of Massachussetts at Lowell and California at Riverside. The lab currently has one post-doc (Dr Sandra Hasenkamp) and two PhD students (Mrs Karen Russell, Mr Imran Ullah) and currently at any time between 1-4 undergraduate students.

Previous laboratory members;

PhD:     Eleanor Wong (Graduated 2011)

MSc:    Caroline Marshall (2008), Rebecca Knight (2008), Adam Worton (2009), Adrian Martin (2010), Robyn Kent (2011), Jolande Jefferson (2012)

Undergraduate (Medicine):    Mohammed Quadri, Neil Amison, Daniel Monnery, Srdjan Milic (Wellcome Trust Biomedical Vacation Scholarship), Laura Denman, Oliver Devine (Wellcome Trust Biomedical Vacation Scholarship), John Nathan Spence, Joshua Kearsley.

Undergraduate (Life Sciences): Emma-Louise Meredith, Anthony Harper, Adam Sidaway (Nuffield Foundation Summer Scholarship), Richard Roye, Taiwo Frank-Isewon.

Visitors: Mathilde Andre (IUT Saint Brieuc, France)

Horrocks laboratory photowall:

Our laboratory is supported financially by awards from the Biotechnology and Biological Sciences Research Council, Royal Society, North Stafforshire Medical Institute, Keele University, Wellcome Trust and Nuffield Foundation.

If you are interested in exploring opportunities to join my research laboratory, please contact me at p.d.horrocks@keele.ac.uk.

My primary teaching and learning role is delivered through the coleadership of the year 4 cohort in the School of Medicine. Year 4 students are located in a variety of healthcare providers throughout Staffordshire and Shropshire. I have extensive experience as a PBL tutor in the pre-clinical years 1 and 2 of Medicine.

I provide undergraduate projects (experimental and non-experimental) as well as honours essay titles for the School of Life Sciences. Here I also contribute to the delivery of the MSc in Molecular Parasitology and Vector Control in conjunction with partners at Manchester and Salford Universities. I also act as a home tutor for students engaged on the MRes in European Scientific Research Training

• March 2012 Medical Research Council industrial CASE studentship with Charnwood Molecular Ltd (36 months £109,288) to Mark Skidmore (P Horrocks, S. Allin, EA Yates and MJ McKenzie as coinvestigators). Novel glycotherapeutics for Alzheimer's disease
• May 2011 Royal Society Research Grant (12 months £14,870) to P. Horrocks and S Hasenkamp. Development of a rapid, simple and sensitive luciferase-based growth assay for the high throughput screening of antimalarial drugs.
• May 2011 Wellcome Trust Biomedical Vacation Scholarship (2 months, £1440) Evaluation of a stably integrated luciferase reporter cassette in Plasmodium falciparum for use in high throughput screening of antimalarial drugs.
• May 2011 Nuffield Foundation Summer Scheme (2 months, £1440 with Sandra Hasenkamp) Optimization of parameters for a luciferase-based luminescent assay for high throughput screening of antimalarial drug action.
• Jan 2011 Keele University Innovation Funding (12 months £10,000) to M. Skidmore, S. Allin, P Horrocks, K Haxter and P Procter. Novel Therapeutics for Severe Malaria - chemically modified, carbohydrate based, polymeric inhibitors of rosetting.
• Jan 2010 North Staffordshire Research Institute Award (24 months £7,100) to P Horrocks and S Allin. An evaluation of the novel bis-indole alkaloid buchtienine as an antimalarial drug
• Dec 2009 BBSRC New Investigator Award (36 months, £428,431). Identification, validation and therapeutic potential of cis-trans interactions that direct coordinated gene expression in Plasmodium falciparum.
• Apr 2009 Wellcome Trust Biomedical Vacation Scholarship (2 months, WTD004448, £1440) An evaluation of magnetic nanoparticle-mediated delivery of exogenous DNA into the human malarial parasite Plasmodium falciparum
• Jan 2008 North Staffordshire Research Institute Award (12 months £10,000) to SJ Chakravorty and P Horrocks. An investigation of the role of Plasmodium falciparum infected erythrocyte knobs in mediating endothelial damage during cytoadhesion.
• Sept 2007 Royal Society Conference Award (A4504-A365) £923 to attend and present at Woods Hole Molecular Parasitology Meeting.
• Sept 2005 Royal Society UK Relocation Fellowship (12 months, 502014.K515/LT/sm, £54,105) Histone modifications and their role in P. falciparum transcriptional regulation.