Doctoral student - Mechanisms of intercellular mitochondrial transfer in alzheimer's disease - Hiring in process/Finished, not possible to apply

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 be working in the research group led by Professor Maria Ankarcrona, belonging to the Division of Neurogeriatrics at the Department of NVS. Our group is based in the new research building BioClinicum in Solna. BioClinicum is connected to the hospital and the Karolinska Institutet's new research house BioMedicum.

The Ankarcrona Lab currently consists of five people with different academic levels and backgrounds, educationally as well as culturally. The focus of the research group is the understanding of mitochondrial dysfunction mechanisms leading to synaptic alterations and neurodegeneration, and the search for mitotherapeutics with potential to reach clinical studies. The current projects on the lab are focus on i) the study of mitochondria-endoplasmic reticulum (ER) contact sites and how these structures affect synaptic function and inflammasome activation; and ii) the transfer of mitochondria between neuronal cells. Along the past years Ankarcrona group has done important discoveries in the field of mitochondria and Alzheimer´s disease such as the identification of the pathways by which amyloid-β internalize in mitochondria and the discovery of new modulators of mitochondria-ER contact sites (Hansson Petersen et al. 2008 PNAS, Hedskog et al. 2013 PNAS, Filadi et al. 2018 Current Biol.; Naia et al. 2021 BMC Biol.)

The doctoral student will be working under supervision of Professor Maria Ankarcrona and Assistant professor Luana Naia.

The doctoral student project and the duties of the doctoral student

Mitochondrial dysfunction has been recognized as an early pathological event in Alzheimer´s disease brain. Data from our lab combining transcriptomic and functional studies in an AD mouse model revealed early mitochondrial dysfunctions very localized at pre-synaptic terminals associated with deficits on axonal mitochondrial transport. Therefore, neurons may benefit on strategies to increase healthy mitochondrial pool in axonal terminals and astrocytes are potential donors. The propose of this doctoral education project is to increase the current knowledge of the molecular mechanisms regulating mitochondrial transfer between astrocytes and neurons under physiology and Alzheimer´s disease conditions. The doctoral student will work with in vitro and in vivo models and cerebrospinal fluid from Alzheimer’s Disease patients which emphasises the translational nature of the project. The specific aims of the doctoral project are to:

1. Elucidate in vitro mechanisms underlying mitochondrial transfer through extracellular vesicles and tunneling nanotubes between astrocytes to neurons.
2. Understand the neuroprotective potential of mitochondrial donation in vitro and in vivo.
3. Evaluate the presence, function and provenience of circulating mitochondria isolated from cerebrospinal fluid of AD models and patients with a spectrum of cognitive deterioration.

The project plan includes a wide spectrum of methods including advanced molecular techniques, functional analysis of mitochondria, imaging methods ranging from high-resolution fluorescence microscopy to electron microscopy, mice manipulation and transplantation and behavioral analysis. The broad and translational nature of the project offers the student an advanced knowledge in neurobiology and mitochondrial function and dynamics, a state of art knowledge in Alzheimer’s Disease, from mechanisms to clinical features and treatment possibilities.

The doctoral student is expected to design and conduct research with the help of the supervisors, and eventually become an independent scientist. The student should also participate as often as possible in the research events organized by the Department and Division such as journal clubs and PhD seminars, attend to national and international meetings and doctoral courses in the scope of the research project.

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:

1. have been awarded a second-cycle/advanced/master qualification (i.e. master degree), or
2. 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
3. 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 seeking a highly talented, creative, and enthusiastic doctoral candidate. The successful candidate must meet the KI requirements for doctoral education, with a strong background in the fields of neurobiology, metabolism and/or mitochondria. The successful candidate should also have relevant wet-lab experience and be self-motivated and able to keep herself/himself informed on developments of the relevant research field, have excellent communication skills in English (both written and spoken), organizational skills, and the ability to work productively and dynamically in a team.

Good knowledge and expertise in methods that will be used specific to this project would be highly advantageous. Specifically, previous practical experience with molecular biology techniques, confocal microscopy, primary cultures and co-cultures, minor surgery and behavior analysis in rodents and/or bioinformatics are considerable substantial merits.

Terms and conditions

The doctoral student will be employed on a doctoral studentship maximum 4 years full-time.

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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.

Read more about the research group:

• - Maria Ankarcrona group | Karolinska Institutet (ki.se)

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