Researcher in Obesity and Pain Biology Full-time

Researcher Position in Madsen Group

We are seeking a highly motivated and dynamic researcher with expertise in in vivo studies, mass spectrometry, and AAVs in the Madsen Group. The position is a 3-year position to start September 1, 2026, or after agreement.

Our group and research The group is centered around understanding protein-protein interactions with a focus on PDZ interactions and the function of the synaptic PDZ domain protein PICK1. PICK1 is an attractive molecular target in drug addiction and pain. Using our expertise on PICK1 and PDZ interactions, we developed and patented the first small molecule inhibitors for this type of proteins together with Neurosearch A/S (Thorsen*, Madsen* et al PNAS 2010). We subsequently solved the PICK1 structure (Karlsen et al, Structure, 2015) and developed a novel quantitative method for assessing binding of scaffold proteins to membrane proteins in their native membrane environment (Erlendsson…Madsen, eLife, 2019). Together, these efforts have enabled the rational design and patenting of bivalent, high-affinity inhibitors to potently target PICK1 in pain and addiction. Inhibition of PICK1 is unique in the sense that it selectively targets the hyperexcitable transmission characterizing these pathologies without affecting overall transmission (Christensen…Madsen, EMBO Mol. Med., 2020; and Jensen et al, Frontiers in Cell. Neu. 2022). In concordance with the involvement of PICK1 in addiction, we have demonstrated that iv administration of the PICK1 inhibitor reduces cocaine craving in a rat model of reinstatement (Turner et al, Neuropharm, 2020). We have refined the development of a small dimeric peptide and virally expressed inhibitors of PICK1 and their effect in mouse models of inflammatory and neuropathic pain (Jensen et al, JCI Insight, 2024 and Noes-Holt et al, BioRxiv, 2023 – in revision for Cell Reports Medicine). Both manuscripts have led to IDFs and subsequent patent applications (P5521EP00 and P5457EP00) and the establishment of the spin-out company Zyneyro.

In a parallel effort, we discovered a regulatory role of PICK1 in maturation of dense core vesicles in the pituitary and pancreatic beta-cells (Holst*, Madsen* et al, Plos Bio, 2013). This has led us to the subsequent identification of a functional role of PICK1 in the storage/release machinery in neurons and chromaffin cells. We followed these findings up describing the molecular mechanism by which PICK1 is recruited to lipid membranes of high curvature (Herlo…Madsen, Cell Reports, 2018) and showing the translational relevance of these findings by describing 4 coding variants in PICK1 identified in patients with type 2 diabetes that modulate insulin processing in beta-cells (Andersen et al, JCI, 2022). Work performed in collaboration with Christoffer Clemmensen has most recently demonstrated the s.c. administration of the PICK1 inhibitor provides weight reduction in Diet Induced Obese mice (Science Adv. 2024).

We are currently combining omics approaches with intravital microscopy to characterize and understand the molecular mechanism underlying the potent effect of inhibiting the target proteins PICK1 in peripheral neurons in neuropathic pain models and obesity. Furthermore, we use whole-brain cFOS light sheet microscopy and a novel analytical tool together with neurotransmitter biosensors and systems neuroscience approaches to untangle the interoceptive (Brain-body communication) aspects following from inhibition of PICK1 in these conditions.

Project description Obesity prevalence has doubled over the past 30 years, substantially compromising quality of life and imposing a major burden on global economies. Although highly effective incretin-based anti-obesity treatments are currently available, they remain imperfect, as they are associated with significant loss of lean mass in addition to fat mass, as well as adverse effects such as nausea. We have identified the scaffolding protein PICK1 as a novel therapeutic target; its inhibition using a bivalent peptide has shown promising anti-obesity effects. Notably, this treatment does not induce lean mass loss or nausea. The present project aims to achieve a deeper understanding of PICK1 biology in sensory neurons and its relation with adipose tissue, with a particular focus on obesity-related differences, with the ultimate goal of improving current anti-obesity therapies.

Job description Your responsibilities will include conducting pull-down mass spectrometry studies as well as global proteome and phosphoproteome experiments, together with AAVs injections, tissue dissection and immunohistochemistry. In addition, we favour experience with generating and maintaining mouse models, performing and designing behavioral experiments, phenotypical characterization of genetic mouse models with a focus on Diet-Induced Obese models, and establishing conditional knock-out lines. You are expected to coordinate these efforts within the group among 4-5 researchers as well as oversee collaboration and coordination with researchers within the department and external collaborators. Furthermore, you are expected to disseminate the results at seminars, international conferences and for the general public.

Profile We are looking for a highly motivated and enthusiastic scientist with the following competencies and qualifications:

• PhD in neuroscience or a related field
• Minimum of 4 years postdoctoral research experience
• Extensive experience in mice models of obesity and pain as well as behavioral and phenotypic characterization
• Experience in generating and maintaining new transgenic and knockout mouse models,
• Fine tissue dissection, mass spectrometry, and deep knowledge in biochemistry techniques as well as immunohistochemistry.
• AAV design and biochemical production/purification
• Demonstrated ability to conceptualize and design innovative research projects aligned with the group's focus areas
• International experience and a strong capacity for establishing collaborations and networking.
• Proven leadership skills, including teaching and supervising students and researchers at various levels, along with strong project management
• Strong publication record, showcasing scientific productivity in peer-reviewed journals
• Proven track record of science communication skills for both scientific audiences and the general public

General criteria apply to the appointment of researcher at the University of Copenhagen. The criteria (research, teaching, Innovation & Societal Impact, organizational contribution and leadership) are considered as a framework for an overall assessment of the applicant. In addition, each applicant will be assessed according to the specific requirements listed in this advertisement.

Place of employment The place of employment is at the Department of Neuroscience Faculty of Health and Medical Sciences, University of Copenhagen. We offer creative and stimulating working conditions in dynamic and international research environment. Our research facilities include modern laboratories and highly collaborative working environment.

Terms of employment The average weekly working hours are 37 hours per week.

The position is a fixed-term position limited to a period of 3 years. The start date is 01/09-26 or after agreement.

Salary, pension and terms of employment will be in accordance with the agreement between the Ministry of Finance and AC (Danish Confederation of Professional Associations). Depending on qualifications, a supplement may be negotiated.

Non-Danish and Danish applicants may be eligible for tax reductions, if they hold a PhD degree and have not lived in Denmark the last 10 years.

The position is covered by the “Memorandum on Job Structure for Academic Staff at the Universities” of June 28, 2013.

Questions For further information please contact Assistant Professor Kenneth Lindegaard Madsen at kennethma@sund.ku.dk . For questions regarding the recruitment procedure, please contact SUND HR.

International applicants may find these links useful www.ism.ku.dk (International Staff Mobility) and https://www.workindenmark.dk/ .

Application procedure Your online application must be submitted in English by clicking 'Apply for position' below. Furthermore, your application must include the following documents/attachments – all in PDF format:

• Motivated letter of application (max. one page)
• CV incl. education, work/research experience, language skills and other skills relevant for the position
• A certified/signed copy of a) PhD certificate and b) Master of Science certificate.
• List of publications

Application deadline 1 July 2026, 23.59pm CET We reserve the right not to consider material received after the deadline, and not to consider applications that do not live up to the abovementioned requirements.

The further process After the expiry of the deadline for applications, the authorized recruitment manager selects applicants for assessment on the advice of the hiring committee. All applicants are then immediately notified whether their application has been passed for assessment by an unbiased assessor.

The assessor makes a non-prioritized assessment of the academic qualifications and experience with respect to the above-mentioned area of research, techniques, skills and other requirements listed