Doctoral Candidate Position 11 - H. Lundbeck A/S & University of Aarhus, Denmark

Qualification and rank-ordering of microglia/macrophage targeting principles for potential treatment of Parkinson's Disease

Application form

Description of project

In the BICEPS collaboration the overall hypothesis is that Parkinson's Disease (PD) must be considered as a systemic disease where both the peripheral and central immune response plays a role in the pathophysiology.
In this project we will correlate activation stages of central microglia and peripheral macrophages at the single cell level in an advanced animal model of seeded alpha-synuclein aggregation to the inflammatory state of activated human iPSC derived microglia and macrophages to develop a set-up for qualifying and prioritising targets for potential treatment of PD.
More specifically the student will (i) Define microglia and macrophage subpopulations and their activation states in a well-established alpha-synuclein seeding model in mice (developing progressive alpha-synuclein pathology and microglia activation) at different stages of disease progression using single-cell RNA sequencing and more functional analysis (fx. cytokine analysis) (ii) Compare the transcriptomic profiles to stimulated human iPSC-derived microglia and macrophages in culture to understand what disease stage we can capture in vitro (iii) Rang-order microglia/macrophage targeting principles (small molecules and antibody tools) in vitro based on correction of gene expression and using functional assays (cytokine release and phagocytosis) (iv) Apply the 1-2 most promising principles targeting microglia and macrophages to the in vivo model to build the correlation between the iPSC culture model and the effect on inflammation in vivo (v) Assess the effect of modulating the inflammatory state of microglia/macrophages on alpha-synuclein pathology development using methods based on new antibody tools.
The student will be part of a Neuroscience Research unit specialised in developing new treatments for diseases in the central nervous system. The fundamental methods in the project; the animal model of seeded aggregation and human iPSC differentiation to macrophages and microglia are well-established in our laboratories. The project will furthermore involve biochemical techniques, RNA scope, novel immunocytochemistry methods to detect alpha-synuclein pathology, advanced microscopy, single cell RNA sequencing and functional analysis of macrophages/microglia.

Required selection criteria

Preferred selection criteria

Specific Requirements

Benefits

Eligibility criteria

H. Lundbeck A/S based in Copenhagen, Denmark is one of the only pharmaceutical companies in the world focusing exclusively on brain diseases. With more than 70 years of neuroscience expertise, Lundbeck has developed and commercialized some of the world's most widely prescribed therapies for brain diseases.
We are driven by a culture of innovation, collaboration, and respect. We inspire curiosity, expect integrity, and pursue our achievements through knowledge-sharing, patient engagement, and the passion to deliver our end goal. We understand we carry a huge responsibility for the societies we serve, and use our knowledge and voice to raise awareness, challenge standards, and increase opportunities - for patients and each other. We are at the forefront of treatment innovation, and together we continue to make a difference to people living with brain diseases.
We need every brain in the game, and at Lundbeck, we are committed to building a workforce that is as diverse as the people we serve. Read more about our commitment at this website.
Our selection procedure follows the guidelines of the Recruitment code (NVP) and European Commission's European Code of Conduct for recruitment of researchers.

Selection process

The application and supporting documentation to be used as the basis for the assessment must be in English. Applications should include:

If all, or parts, of your education have been completed abroad, we also ask you to attach documentation of the scope and quality of your entire education, both bachelor's and master's education, in addition to other higher education. Upon request, you must be able to obtain certified copies of your documentation.
Please use the harmonized Application Form before the deadline of 15-February 2025. Candidates are encouraged to apply early. Applications will be accepted until this deadline and considered on a rolling basis until the position is filled.
Applications submitted by post or email will not be considered. Upon request, you must be able to obtain certified copies of your documentation.
In the evaluation of which candidate is best qualified, emphasis will be placed on education, experience, and personal and interpersonal qualities.

Additional comments

Physically the student will be based at H. Lundbeck in Copenhagen. All infrastructure to support preclinical research (in vitro and in vivo) is available at headquarters in Copenhagen. The Research Unit consist of 220 international employees and have a strong student environment of both master and PhD students. We offer you a salary of € 4562 + € 456 (in pension) per month the first year. The salary will be adjusted once a year. In addition, there is 25 days of payed vacation/ year plus 5 days extra/ year after 1 year of work. The position is limited to a period of 3 years. The PhD candidate will be enrolled at the Faculty of Health, Biomedicine, University of Aarhus, Denmark, with Prof. Marina Romero-Ramos as co-supervisor. Some travel between Aarhus and Copenhagen must be anticipated in relation to PhD courses. Aarhus University is an academically diverse and research-intensive university with a strong commitment to high-quality research and education and the development of society nationally and globally. The university offers an inspiring research and teaching environment to its 39,000 students (FTEs) and 8,000 employees, and has an annual revenues of EUR 884 million. Learn more at this website.