Doctoral student position in Targeted cell death and immune modulation in glioblastoma - 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 research group of Sten Linnarsson is located at Biomedicum in the Molecular Neurobiology unit, at the Department for Medical Biochemistry and Biophysics, MBB. The Mol Neuro unit is a highly creative and collaborative environment that shares expertise, equipment, and lab space between groups in the unit. The unit has regular seminars where students and post docs present their work and get feed-back from the unit members.

Linnarsson lab currently consists of 16 members and have a weekly group meeting where members present their work and discuss scientific publications. All students have weekly scheduled meetings with their supervisor and collaborators. All members of the group are encouraged to participate in workshops and conferences and interact with scientists within KI as well as internationally

The doctoral student project and the duties of the doctoral student

The project is a part of a larger effort in the Linnarsson group to create a highly specific therapeutic agent for glioblastoma (GBM). The project advertised here will contribute towards this goal in two ways. Firstly, the project entails finding an optimal mechanism for inducing targeted immunogenic glioblastoma cell death. To this end, the student will perform screenings of well-known cell death inducing proteins and engineered derivatives thereof. This work will be conducted in murine animal models by grafting transfected murine cell lines as well as patient derived GBM organoids. The second aim is to characterize and modulate the immune response evoked by the targeted cell death. Therein, the same GBM models will be leveraged for immunomodulatory factor screening.

To achieve these aims, the student will have to independently perform transfection experiments on cell lines and organoids to help establish glioblastoma animal models with inducible expression of candidate proteins. The readout for protein screening experiments will be mostly microscopy-based. The corresponding duties of the student will entail processing the harvested tissues, performing microscopy and image analysis. More specifically, the student will perform both conventional histology staining and high-throughput single molecule RNA fluorescence in situ hybridization (smFISH) experiments. The student will operate custom microscopes and fluidics systems adapted for smFISH experiments, as well as use and further develop highly automated computational image processing and analysis pipelines.

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

Candidates must have extensive practical experience in fluorescence microscopy. Any experience in technical troubleshooting and maintenance of wide-field microscopes is also advantageous given that the student will mainly work with customized microscopy setups. Similarly, experience in operating and maintaining automated fluidics systems is highly sought after.

Expertise in smFISH methods is necessary, especially pertaining to method development and protocol optimization, as a variety of smFISH modalities might need to be implemented throughout the project. The prospective student is expected to have a general overview of the spatial transcriptomics field and to be able to readily implement optimal chemistry choices (e.g., glass surface coating, tissue clearing, or signal amplification strategies) most suited for different experimental needs. Similarly, candidates should be able to design custom oligonucleotide probes for smFISH experiments. Prior experience with more conventional tissue stainings, such as lectin conjugates, is also desirable.

Experience with mammalian cell or tissue culturing is advantageous but not strictly required. However, given the precious nature of tissue samples to be used in the project, applicants must have experience in handling biological tissues for microscopy purposes (e.g., freezing, cryosectioning).

Applicants must have a firm grasp of Python programming language and prior experience implementing it for image processing and analysis (filtering, segmentation, etc.). Furthermore, general knowledge and basic skills of single-cell transcriptomics analysis methods are required for handling and interpreting smFISH data (e.g., spot-cell assignment, principal component analysis).

Regarding general competences, the student will often be expected to perform laboratory work with minimal supervision but in high collaboration with other group members. Therefore, extensive laboratory work experience as well as excellent communication skills are essential. Given that the project will largely revolve around protein screening in vivo with therapeutic implications, applicants must be prepared to work with utmost diligence and organization regarding both experimental work and data presentation. Lastly, the student will be expected to show a high degree of engagement and original thinking when planning the experiments and reviewing results together with the supervisor and other group members

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.

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