Doctoral (PhD) student position in translational neuroscience: autophagy in Alzheimer's disease

Do you want to contribute to top quality medical research? To be a doctoral student means to devote oneself to a research project under supervision of experienced researchers and following an individual study plan. For a doctoral degree, the equivalent of four years of full-time doctoral education is required. The research group The doctoral student will join Pontus Plavén-Sigray's research team at the Department of Clinical Neuroscience, within Andrea Varrone's research group at the BioClinicum. The team conducts translational research on ageing and Alzheimer's disease, with a focus on drugs that modulate autophagy and mTOR signalling. We combine clinical drug trials, PET imaging and cerebrospinal fluid (CSF) biomarkers with preclinical studies in cell and animal models. The project is carried out in close collaboration with Per Nilsson's research group at the Department of Neurobiology, Care Sciences and Society, which has long experience of autophagy research and of treatment studies in mouse models of Alzheimer's disease. The main supervisor is Pontus Plavén-Sigray. The co-supervisors are Per Nilsson, Jonas Svensson and Makoto Shimozawa. The work takes place in Solna, in an international environment of doctoral students, postdoctoral researchers and research nurses. The doctoral student project and the duties of the doctoral student Impaired autophagy contributes to the accumulation of amyloid-β and tau in Alzheimer's disease, and drugs that activate autophagy, such as the mTOR inhibitor rapamycin, are being evaluated as a possible treatment. The doctoral project examines how activated autophagy affects the degradation and secretion of these proteins, and whether the effect can be tracked with biomarkers in CSF. The project comprises three studies. The first addresses the mechanism in human neuronal cell models treated with compounds that activate or block autophagy. The second tests the findings in vivo in mouse models of Alzheimer's disease, with drug treatment, CSF sampling and analysis of brain tissue. The third analyses proteomics data from human CSF, collected in clinical studies and biobanks, and compares them with the findings in cells and mice. The doctoral student plans and performs the experiments under supervision. The work includes cell culture and drug treatment of cells, treatment studies in mice, CSF sampling, dissection and preparation of brain tissue, immunohistochemistry with confocal microscopy and quantitative image analysis, and biochemical assays of autophagy. It also includes bioinformatic and statistical analysis of proteomics data from mouse and human, scientific writing and presentation of results at conferences. In parallel, the student takes doctoral courses according to the individual study plan. What do we offer? A creative and inspiring environment full of expertise and curiosity. Karolinska Institutet is one of the world's leading medical universities. Our vision is to pursue the development of knowledge about life and to promote a better health for all. At Karolinska Institutet, we conduct successful medical research and hold the largest range of medical education in Sweden. As a doctoral student you are offered an individual research project, a well-educated supervisor, a vast range of elective courses and the opportunity to work in a leading research group. Karolinska Institutet collaborates with prominent universities from all around the world, which ensures opportunities for international exchanges. You will be employed on a doctoral studentship which means that you receive a contractual salary. Employees also have access to our modern gym for free and receive reimbursements for medical care. Eligibility requirements for doctoral education In order to participate in the selection for a doctoral position, you must meet the following general (A) and specific (B) eligibility requirements at latest by the application deadline. It is your responsibility to certify eligibility by following the instructions on the web page Entry requirements (eligibility) for doctoral education. A) General eligibility requirement You meet the general eligibility requirement for doctoral/third-cycle/PhD education if you:

• have been awarded a second-cycle/advanced/master qualification (i.e. master degree), or
• have satisfied the requirements for courses comprising at least 240 credits of which at least 60 credits were awarded in the advanced/second-cycle/master level, or
• have acquired substantially equivalent knowledge in some other way in Sweden or abroad.*

Follow the instructions on the web page Entry requirements (eligibility) for doctoral education. *If you claim equivalent knowledge, follow the instructions on the web page Assessing equivalent knowledge for general eligibility for doctoral education. B) Specific eligibility requirement You meet the specific eligibility requirement for doctoral/third-cycle/PhD education if you:

• Show proficiency in English equivalent to the course English B/English 6 at Swedish upper secondary school.

Follow the instructions on the web page English language requirements for doctoral education. Verification of your documents Karolinska Institutet checks the authenticity of your documents. Karolinska Institutet reserves the right to revoke admission if supporting documents are discovered to be fraudulent. Submission of false documents is a violation of Swedish law and is considered grounds for legal action. (A) and (B)can only be certified by the documentation requirement for doctoral education. Skills and personal qualities We are looking for a motivated individual with a strong experimental background and a clear interest in neurodegenerative diseases and translational research. You work in a structured and meticulous manner, possess strong organizational skills, and are comfortable taking initiative and working independently while collaborating effectively with others. Qualifications We are looking for someone who has:

• A Master's degree or equivalent in biomedicine, molecular biology, neuroscience, or another relevant field.
• Documented hands-on experience of experimental work with rodents in a laboratory setting.
• Experience with cell culture and basic molecular biology techniques.
• Excellent communication skills in English, both written and spoken.

Particularly meritorious Particular emphasis will be placed on documented experience in:

• Drug treatment in rodents, in particular with mTOR inhibitors or other autophagy-inducing compounds.
• Experimental work with rodent models of Alzheimer's disease.
• Collection of cerebrospinal fluid (CSF) samples from rodents.
• Cell-based studies involving autophagy-modulating compounds.

Meritorious Experience in the following areas is also considered an advantage:

• Brain dissection, and extraction and preparation of brain tissue for histological and biochemical analyses.
• Immunohistochemistry, confocal microscopy, and quantitative image analysis.
• Bioinformatic analysis of proteomics data, including quality control, integration of multiple datasets, and comparisons between animal and human data.
• Analysis and interpretation of biomarker or proteomics data from human or animal CSF samples.
• Culture of human stem cell-derived neural cells and primary cell cultures.
• Western blot, qPCR, immunocytochemistry, and cryosectioning.
• Certification in laboratory animal science.
• Co-authorship of scientific publications.

Terms and conditions The doctoral student will be employed on a doctoral studentship maximum 4 years full-time. Application process Submit your application and supporting documents through the Varbi recruitment system. Use the button in the top right corner and follow the instructions. We prefer that your application is written in English, but you can also apply in Swedish. Your application must contain the following documents:

• A personal letter and a curriculum vitae
• Degree projects and previous publications, if any
• Any other documentation showing the desirable skills and personal qualities described above
• Documents certifying your general eligibility (see A above)
• Documents certifying your specific eligibility (see B above)

Selection A selection will be made among eligible applicants on the basis of the ability to benefit from doctoral education. The qualifications of the applicants will be evaluated on an overall basis. Karolinska Institutet uses the following bases of assessment:

• Documented subject knowledge of relevance to the area of research
• Analytical skill
• Other documented knowledge or experience that may be relevant to doctoral studies in the subject.

All applicants will be informed when the recruitment is completed. KI applies a salary scale when setting salaries for doctoral students. Department of Clinical Neuroscience Your career continues here Want to make a difference? Join us and contribute to better health for all