Two phd positions: Immunity/ genomics (UK)

Two graduate student positions.  Details below.

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Genomic imprinting (GI) is the inactivation of one allele in diploid
individuals, with inactivation being dependent upon the sex of the
parent from which it was derived. Natural selection is expected to
favor expression of both alleles in order to protect against recessive
mutations that render a gene ineffective. What, then, is the benefit of
silencing one copy of a gene, making the organism functionally haploid at
that locus? HaigĄĶs kinship theory is the current leading evolutionary
explanation.

Although current observations support the kinship theory, there have
been no independent tests. Eusocial Hymenoptera (ants, bees and wasps)
are an ideal model systems for making truly independent a priori tests of
the theory. Hymenoptera are haplodiploid, with diploid females (queens
and workers) arising from fertilized eggs and haploid males arising
from unfertilized eggs. This different genetic system combined with the
shared brood rearing and reproductive division of labour characteristic of
eusociality results in range of novel predictions for the kinship theory.

One previous problem in using Hymenoptera to test the conflict theory was
that they were not known to have the mechanisms required for genomic
imprinting. In 2006, it was shown that Apis mellifera has a fully
functioning cytosine-phosphate-guanine (CpG) methylation system. DNA
methylation is one of the major mechanisms of genomic imprinting in
mammals and angiosperms. The honeybee methylation system has been shown
to transmit epigenetic information. CpG methylation has since been shown
to be common in hymenoptera and the Mallon lab have found it in bumblebees
and shown it is invovled in traits predicted by the kinship theory.

Aims and objectives: The major aim of this PhD is to establish
that genomic imprinting occurs in a more tractable bee species, the
bumblebee. Genomic imprinting has not yet been discovered in insects
and this will be a major discovery.

Funding Notes:

This studentship is one of a number of fully funded studentships available
to the best UK and EU candidates available as part of the NERC DTP
CENTA consortium.

For more details of the CENTA consortium please see the CENTA website:
www.centa.org.uk

Applicants must meet requirements for both academic
qualifications and residential eligibility:
http://www.nerc.ac.uk/funding/application/studentships

Please direct informal enquiries to the project supervisor
(ebm3@le.ac.uk).

If you wish to apply formally, please do so via:
http://www2.le.ac.uk/study/research/funding/centa/how-to-apply-for-a-centa-project

Deadline for official application 31st January 2014

References:

Wang et al. (2006). Functional CpG methylation system in a social
insect. Science, 314(5799), 645-647.

Kucharski et al . (2008). Nutritional control of reproductive status in
honeybees via DNA methylation. Science 319, 1827ĄV1830

Foret et al . (2012). DNA methylation dynamics, metabolic
fluxes, gene splicing, and alternative phenotypes in honey
bees. Proc.Natl. Acad. Sci. USA 109, 4968ĄV4973.

Herb et al .(2012) Reversible switching between epigenetic states in
honeybee behavioral subcastes Nature Neuroscience 15(10) 1371-1373


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PhD position

The role of host immune gene expression and gut microbiome in the
anti-trypanosome response of an important insect pollinator

Supervisors: Dr Eamonn Mallon and Prof. Mike Barer

The insect immune system is hugely important to human health and
wellbeing. Whether we consider the immune response of a human disease
vector, or the immune system of an important crop pollinator defending
itself from parasites, an understanding of these systems is vital. A
recent development in this field is the discovery of the role of the
commensual gut bacteria (gut microbiota) in modulating the immune response
of insects to invading parasites.

How the insect gut microbiota help defend against parasites is
largely unknown. The bumblebee Bombus terrestris and its invading gut
trypanosome Crithidia bombi make an excellent model to tease out this
process. Using RNA-Seq the Mallon lab have found 471 bumblebee genes that
are differentially regulated upon infection with Crithidia. The lab has
begun the functional analysis of these genes by knocking them down using
RNAi and seeing the effect on Crithidia levels. It has also been found
that gut microbiota are also important in this defence. When bacteria are
removed through antibiotics, bumblebees are much more highly infected by
Crithidia. If the gut microbiota is restored, bumblebees show a normal
level of Crithidia infection.

This PhD will begin by using RNA-Seq to understand bumblebee gene
expression changes in Crithidia infected bees with and without their gut
microbiota and bacteria gene expression changes in infected and uninfected
bees. We will analyse this RNA-Seq data in four related ways. First we
will look for differentially expressed genes using edgeR. We will also
examine differential exon usage. From our preliminary RNA-Seq experiment,
we have 79 genes that show differential exon using DEXSeq. DEXSeq will
also be used to analyse data from this project. Thirdly, by carrying
out cluster analysis of the differentially expressed (DE) genes across
all time points we can better understand the pathways involved in the
immune response. Initially we will use the clustering algorithm K-means
with Euclidean distance, in the R package flexclust. The expression
data can also be analysed at a systems level using network analysis. We
will use the Weighted Gene Coexpression Network Analysis (WGCNA) in R
to construct the network from gene expression data. Network analysis
takes a more global view by looking directly at the coexpression of all
transcripts under the different treatments.

This project will involve the use of RNA-Seq, Bioinformatic analysis,
qPCR, RNAi, and culturing of gut microbiota

The application procedure and eligiblity are detailed here
http://www2.le.ac.uk/colleges/medbiopsych/research/Postgraduate%20Opportunities/mitbp-at-the-university-of-leicester

Informal enquiries should be directed to Eamonn Mallon ebm3@le.ac.uk
The deadline for formal applications is the 31/01/2014