Aarhus University (AU)

Phd position in "Nanobody-based inhibition of allergen-mediated anaphylaxis"

Aarhus University (AU)

Aarhus C, Denmark

Applications are invited for a PhD fellowship/scholarship at Graduate School of Science and Technology, Aarhus University, Denmark, within the Engineering programme. The position is available from 1 August 2020 or later.

Title
Nanobody-based inhibition of allergen-mediated anaphylaxis

Research area and project description
Allergy is a disease in which the immune system reacts heavily to environmental triggers, allergens, that are generally harmless but exhibit the potential to activate effector cells via IgE-mediated receptor cross-linking. In the last years, molecular approaches enabled us to identify and characterise a number of novel allergens and to assess the clinical relevance of these proteins. Improved understanding of the patient´s reactivity profiles we can now develop strategies for optimisation of specific immunotherapy, design of hypoallergenic protein variants and advanced targeting approaches.

For severe hypersensitivities such as allergies to insect venom, molecular information can help to sharpen our understanding of antibody responses to immunogenic epitopes and to understand the clinical relevance of individual target structures. Complementary we aim for analyses of the interaction of allergens with allergen-specific antibodies and their receptors. In that context we use combinatorial approaches backed with recombinant antibody technologies to establish tools with specificity to clinically relevant antigen.

IgE is an extraordinarily powerful isotype that exhibits highest affinities and exerts strong immune reactions to lowest amounts of target structures. Elucidating the molecular events of interaction can help to understand the nature of the interplay of the immune system with antigens and thus to develop strategies for advanced intervention.

In the PhD project funded by the Novo Nordisc foundation, the applicant will develop, characterise and apply nanobodies and engineered derivatives thereof using a broad set of techniques for dissecting and interfering with the allergic response. The project will involve interactions with national and international research groups in Denmark and Germany as well as companies in the field.

The successful candidate will join the Immunological Biotechnology group headed by Edzard Spillner. The lab´s research focus is the molecular access to a given disease and a mechanism-driven development of biologicals at the interface of immunology, protein biochemistry, biotechnology, and chemistry. With understanding of molecular functions, structures and interactions the design of biologicals will offer opportunities for patient tailored, precision medical treatment.

The project will develop from previous work of our group in the field, e.g.
References:

  • Jensen et al., Structure of intact IgE and the mechanism of ligelizumab revealed by electron microscopy, Allergy, 2020.
  • Jabs et al., Trapping IgE in a closed conformation by mimicking CD23 binding prevents and disrupts FceRI interaction, Nature Communications, 2018 9, 7.
  • Perez Riverol et al., Venoms of Neotropical wasps lack cross-reactive carbohydrate determinants enabling reliable protein-based specific IgE determination, J Allergy Clin Immunol, 2018 141, 1917.
  • Spillner et al., Hymenoptera allergens: from venom to “venome”, Front Immunol, 2014, 5, 77.
Qualifications and specific competences
Applicants to the PhD position must have a recent relevant Master’s degree in Biotechnology, Molecular Biology, or related fields, with an excellent exam record and experience in protein engineering, immunology, or other relevant disciplines. The student is expected to develop and apply nanobodies for interfering with allergic conditions in allergic individuals. Therefore, a keen interest in molecular biotechnology and structural understanding of biomolecules is essential. An open and team-oriented mind and proven abilities in protein biotechnology, combinatorial biotechnologies and structural biology are beneficial.

Applicants able to start sooner than 1 August 2020 are encouraged to indicate so in their application.

Place of employment and place of work
The place of employment is Aarhus University and the work place will be at Department of Engineering, Gustav Wieds Vej 10, Aarhus C at the Aarhus University main campus, in the Immunological Biotechnology group.

Contacts
Applicants seeking further information are invited to contact:
Assoc. Prof. Edzard Spillner, e.spillner@eng.au.dk

Important information for applicants
To be eligible for this PhD position, the candidate must comply with GSST admission requirements.

Applications are received until 1 May 2020 at 11:59 AM (noon) CEST.

To read more, please see the GSST Application Guide.

To apply, please go to the specific project announcement on the GSST website.

Please apply via recruiter’s website.