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  Infection and selection in indigenous East African cattle


   School of Biological Sciences

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Prof M Woolhouse Dr S Knott  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

Interested individuals should email [Email Address Removed] directly. Send a two page Curriculum Vitae including contact details for two academic referees; a one page statement of research interests and grades/transcript of marks.

The Infectious Diseases of East African Livestock (IDEAL) project is producing unique data on the life histories and infectious disease burdens of a cohort of 500 indigenous cattle in Western Kenya. It is a collaborative project between the University of Edinburgh, the International Livestock Research Institute (ILRI) and other national and international partners. The overall aim is to generate a better understanding of the genetic and phenotypic factors that allow these animals to tolerate a massive infectious disease pressure in an environment where there is minimal use of vaccination or other preventive measures. This knowledge will ultimately inform breed improvement programmes (which have been repeatedly attempted in the study area) aiming to increase food security by increasing productivity, especially milk yields.
The project will integrate genetic analyses based on high-density (>400,000) SNP profiles for every cow in the study and epidemiological analyses based on histories of infection with over 30 different pathogen species. Whole genome sequences are available for a small subset of animals. There is epidemiological evidence that infectious diseases (including East Coast fever, trypanosomiasis and heartwater) exert strong selection pressure on the study population. We now wish to identify signatures of selection in the SNP data. Selection is likely to have occurred over two timescales: 1) in the last 10-20 years when there has been significant cross-breeding between European taurines and the indigenous population; and 2) over the past 1000+ years since Asian zebu cattle were interbred with African taurines. Appropriate analyses are expected to include admixture mapping, candidate gene studies, localisation of QTL, and genome scans for signatures of hitchhiking events. Particular attention will be paid to identifying pathways containing an excess of genes in genome regions under selection. Previous work suggests several candidate pathways, including MAPK signalling and cholesterol metabolism. The cholesterol pathway plays an important intrinsic role in host defence against infection via a pathway molecularly coupled to innate immunity. These studies underscore key host protection pathways in infection that can help inform planned genetic investigations.
The successful applicant will have a biological sciences degree, either a 1st or 2i, and possibly an MSc in population genetics or biological computation. An interest in and some experience of statistical analysis of biological and/or genetic data is important. Training will be provided in the state-of-the-art methodologies in statistical genomics and pathway analysis, involving analysis of SNP data and interrogation of genome sequences, backed up by access to our taught MSc in Quantitative Genetics & Genomic Analysis. Access to, and training in the use, of high performance computing facilities (including the part BBSRC-funded HECToR machine) will be provided. The student will spend time working in 2 very active research group studying epidemiology and genetics and pathway biology of infection – these will provide a very supportive intellectual environment. Some field work in Kenya may also be required. This will be arranged through ILRI, which has structures in place to support visiting research students.

Funding Notes

This opportunity is only open to UK nationals (or EU students who have been resident in the UK for 3+ years) due to restrictions imposed by the funding body.

References

Blanc, M. et al. (2011). Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis. PLoS Biol. 9: e1000598.
Cheesman, S. et al. (2010) A single parasite gene determines strain-specific protective immunity against malaria: The role of the merozoite surface protein I. Intl J. Para. 40: 951-961.
Mazein, A. et al. (2011) Regulation and feedback of cholesterol metabolism. Nat. Preceed. doi:10.1038/npre.2011.6315.1
Noyes, H. et al. (2011). Genetic and expression analysis of cattle identifies candidate genes in pathways responding to Trypanosoma congolense infection. Proc. Natl Acad. Sci. USA 108: 9304-9309.

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Project supervisors

Career overview

Mark Woolhouse is a Professor of Infectious Disease Epidemiology at the Usher Institute, part of the College of Medicine and Veterinary Medicine at the University of Edinburgh. They have a significant academic background in the field of infectious diseases and epidemiology. Their research focuses on understanding the dynamics of infectious diseases and the impact of public health interventions. Mark Woolhouse has contributed to the development of mathematical models that inform disease control strategies and has been involved in various research projects aimed at improving global health outcomes.


Research interests

Mark Woolhouse's research focuses on infectious disease epidemiology. They are particularly interested in the dynamics of infectious diseases, including the transmission and control of pathogens. Their work encompasses various aspects of epidemiology, including modelling disease spread, understanding the impact of interventions, and exploring the relationship between human behaviour and disease dynamics.

View Professor Mark Woolhouse's profile 
Career overview

Sara Knott obtained a PhD from the University of Edinburgh at the AFRC Institute of Animal Physiology and Genetics Research between 1986 and 1990. Following this, they worked as a postdoctoral researcher at the University of Edinburgh from 1990 to 1996. From 1996 to 2006, they held the position of Royal Society University Research Fellow at the same institution. They were also a RCUK Fellow from 2005 to 2010. Since 2007, they have been a Reader at the Institute of Evolutionary Biology at the University of Edinburgh.


Research interests

Sara Knott's research focuses on understanding the genetic control of complex traits that underpin variation of medical, evolutionary, and commercial relevance. They investigate how individual genes act and interact with each other and the environment, utilising dense SNP genotypes or sequence data to dissect this variation.

View Dr. Sara Knott's profile