We have the following 11 month internships available, commencing September 2024. We welcome applications from students who are currently studying a relevant undergraduate science degree with optional professional training year (this will usually be between the second and third year of the degree). The salary for our 2024 internships will be approximately £22,400 (11 months pro rata).
You may apply for one project only. Our internships require students to have an unrestricted right to work in the UK.
TO APPLY: To apply for an internship, please complete an Internship Application Form and return to firstname.lastname@example.org. Ensure you include the reference number and title of the project you are applying for. Closing date to apply: 26.02.24 (midnight)
Investigating the use of modified glycan receptors by avian influenza viruses.
|Dr Thomas Peacock
Avian influenza viruses (AIVs) have caused three of the last five respiratory virus pandemics. However, AIVs replicate very poorly in humans and must substantially mutate and adapt to efficiently infect and transmit between humans. Influenza viruses use glycan receptors to enter host cells (specifically glycans with the terminal sugar sialic acid, called sialylated glycans). The type and distribution of these sialylated glycan receptors differ between birds and humans. AIVs must learn to use the human-like receptors to go pandemic.
We have recently found that several chicken-adapted AIVs are considered to have pandemic potential do not bind the typical avian-like sialylated glycan receptors and instead only bind these receptors when they are modified through addition of a sulphate side chain. It appears this property has evolved multiple times in highly chicken-adapted AIVs, but not seen in ducks; which are thought to be the natural reservoir of AIVs. This research suggests that this is the preferred sulphate, sialylated glycan and gives a fitness advantage in a chicken host. Full details and how to apply
Annotation and functional characterisation of Capripoxvirus Genes.
Capripoxviruses (CPPVs) cause debilitating disease in animals. There are three CPPVs: lumpy skin disease virus (LSDV), sheep pox virus and goat pox virus. LSDV preferentially infects cattle and water buffalo, but not in sheep or goats or other livestock. Viral determinants of CPPV host-specificity are unknown and the evolution of CPPV genes in relation to other poxviruses is poorly documented. This means the availability of >3,600 poxvirus and 151 CPPV complete genomes offers an exciting opportunity to deliver novel insights into CPPV biology. The main goal is to create a consistent nomenclature for CPPV genes reflecting their wider evolutionary history among poxviruses. In this project you will use bioinformatic methods to identify and characterise the CPPV core genome (genes present in all CPPVs) and accessory genome (genes present in only some CPPVs). You will compare this with core and accessory genomes of other poxviruses. About half the genes in any poxvirus genome are accessory and often encode proteins that antagonise host’s antiviral defences and therefore, are key determinants of virus tropism. You will also generate reagents to test further candidate genes determining CPPV tropism identified by the bioinformatic analysis. This project will help discover the viral determinants of CPPV host-specificity and pave the path towards the genetic engineering of CPPVs for vaccine development. Full details and how to apply
Understanding essential host factors for FMDV replication in pigs and cows: Towards gene edited FMD resistant livestock.
Foot-and-mouth disease virus (FMDV) is the causative agent of foot-and-mouth disease (FMD). This is a highly infectious virus that causes blisters on the feet and mouth of cloven hooved animals such as pigs and cattle. It also reduces the lifetime productivity of the infected animals. FMDV outbreaks impose a significant cost on the global pig and cattle industry, which together are worth £700 billion annually.
As part of an ongoing project, we are investigating on how to create gene edited livestock with resistance to FMDV, as a method to prevent outbreaks of the disease. In this project, we have identified several host genes essential for FMDV replication in porcine cells, reducing the expression of these genes in porcine cells completely prevented viral replication and making the cells resistant to infection with FMDV. This area of research has reached an exciting stage. The internship will contribute to the project by generating FMD resistant cell lines and characterizing the function of these target genes during FMDV infection. Full details and how to apply
|Identification of viral determinants influencing bluetongue virus infection dynamics in Culicoides biting midges
|Dr Marc Guimera, Dr Simon King & Dr Christopher Sanders
Bluetongue virus (BTV) is an arthropod-borne virus (arbovirus) that causes a severe haemorrhagic disease in domestic and wild ruminants (sheep, cattle, goats, deer, etc.). Bluetongue disease is of significant economic importance in livestock in both intensive agricultural settings and subsistence farming worldwide. The UK is currently facing the threat of BTV incursion due to an outbreak of BTV-3 in the Netherlands in 2023. BTV is transmitted between susceptible animals through the saliva of midges of the genus Culicoides during blood feeding on the animal. Interestingly, different BTV strains display different abilities to infect, replicate and disseminate through the insect, with some viruses reaching the vector’s saliva more efficiently than others. In addition, the capsid shell of the BTV viral particle, which plays a role in initiating infection in target cells, can be partially digested by enzymes found in the gut and saliva of Culicoides. Such modified viral particles can be 100 times more infectious in the midge compared to their respective unmodified particles. Why and how these differences between viral strains and particles influence infection rates and dynamics in the insect vector is currently unknown. Full details and how to apply
|Deciphering the mechanism of attenuation of a novel avian coronavirus vaccine candidate.
|Katalin Foldes, Dr Renata Fleith, Dr Sarah Keep & Dr Trevor Sweeney
The Gammacoronavirus infectious bronchitis virus (IBV) is a highly contagious pathogen of domestic fowl that causes significant production loss across the globe. IBV vaccines are currently generated by serial passage of virulent field isolate through embryonated hens’ eggs; the exact mechanism of attenuation is unknown and there is a risk for reversion to virulence. Methods for rational attenuation are therefore highly desirable for future vaccine development. Our previous research showed that specific modifications in the non-structural proteins (nsps) offer a promising avenue for rational attenuation.
These amino acid changes could both result in attenuated and temperature-sensitive replication phenotype, suggesting that the two phenotypes are linked; however, the mechanism of both is unknown.Full details and how to apply
|Activation-induced markers to identify T cells associated with protection against ASFV
|Dr Priscilla Tng, Selma Schmidt & Dr Chris Netherton
CD4 T-helper cells play a pivotal role in steering adaptive immune responses, particularly in safeguarding against viral infections. Their significance becomes even more pronounced in the defence against African swine fever (ASF), a disease caused by the complex ASF virus (ASFV) that has triggered numerous outbreaks across the globe. ASFV poses a severe threat, inducing a contagious and often fatal disease affecting both domestic and wild pigs. Given the absence of a widely licensed vaccine, disease control relies on drastic measures such as quarantine and culling of infected and exposed animals.
Recent findings suggest a link between vaccine efficacy against ASF and the activity of CD4 T-helper cells. Despite this correlation, the specific characteristics and contributions of individual CD4 T-cell subsets remain elusive. The T-cell biology group has devised an Activation-Induced Marker (AIM) assay utilising multi-parameter flow cytometry tailored to porcine T cells. AIM assays offer the advantage of detecting antigen-specific T cells in live samples, distinguishing them from conventional methods that necessitate fixation for intracellular staining of cytokines. This project will mainly focus on adapting the AIM assay to identify ASFV-primed T cells. This would facilitate a nuanced exploration of the heterogeneous responses orchestrated by CD4 T cells, shedding light on their intricate contributions to protection against ASF. Full details and how to apply
Genome Engineering for Gene Function Study and Improvement of HVT Vector.
|Dr Yaoyao Zhang & Dr Yongxiu Yao
Herpesvirus of Turkey (HVT) is one of the most successful and widely used viral vectors for generation of recombinant vaccines that deliver protective antigens against other avian pathogens. To overcome the interference between individual recombinant HVT vaccines, we have developed triple-insert HVT-vectored vaccine candidate capable of inducing simultaneous protection against multiple avian pathogens. However, the animal experiments showed reduced replication efficiency in chickens, indicating that the insertion of foreign genes affects HVT replication in vivo, and the HVT may not be able to express more than 3 cassettes without compromising on replication thus limiting the induction of immunity. Full details and how to apply
Pathogenesis, immunity, and control of influenza viruses
|Dr Basu Paudyal & Prof Elma Tchilian
Current vaccine strategies against influenza viruses induce strain specific neutralising antibodies but the rapid emergence of variant strains leads to loss of protection, necessitating frequent updating of vaccines. An alternative approach is to target conserved antigens that induce T cell responses, providing the basis for a universal influenza vaccine. Furthermore, seasonal influenza vaccines are administered intramuscularly, although local immunity in the respiratory tract is important in control of respiratory infections.
The pig is physiologically, anatomically genetically and immunologically more similar to humans than small animals and is a natural host for very similar influenza viruses to humans. Furthermore, the lung structure and morphology closely resemble that in humans, and pig antibody responses to influenza have a very similar specificity to humans. In collaboration with the University of Oxford we have shown that a vaccine consisting of conserved internal proteins of the virus, induces T cell responses in the pig influenza model that prevent viral shedding from the nose and reduce lung pathology and lung viral load. Full details and how to apply
The Pirbright Institute conducts a large proportion of its science studies under high containment conditions. It is a condition of employment that no person working at The Pirbright Institute may keep any animals which are susceptible to foot-and-mouth disease or reside at premises where such animals are kept. "Susceptible animals" include cows, sheep, goats, deer, llamas, and all other cloven-hoofed animals. The quarantine period for all Restricted Areas is 72 hours - during this 72 hour period, it is not permitted to have close contact with susceptible animals. In high containment areas, the Institute implements a number of procedures in order to comply with strict biosafety legislation. Access procedures for these areas requires all personnel to undertake a full change of clothes, including the removal of all jewellery and piercings, and completing two full body and hair washes when leaving high containment.
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