Biology Education

Epilepsy is a family of neurological disorders affecting 1% of the general population. About 30% of patients are resistant to current medications, and surgical treatment options are possible for only a minority of selected cases. Pharmacoresistant patients continue to experience seizures throughout their lifetime, with a severe impact on their quality of life. The development of novel and more effective treatment strategies is therefore highly needed, as well as preventive approaches that could block the progression of the disease.
The main objective of this project is to develop highly specific and precise gene therapy approaches that target critical cell populations involved in the development of epilepsy and seizures. By using a combination of advanced molecular biology, electrophysiological and imaging techniques, we will (i) identify hyper-active neuronal ensembles involved in the early stages of epileptogenesis, (ii) characterize their location, molecular identity and functional alterations, (iii) apply gene therapy approaches designed to limit the functional output of hyper-active neurons and prevent the development of chronic epilepsy. These approaches will be validated in different animal models of epilepsy, and will provide important new knowledge on the mechanisms of epileptogenesis, as well as basis for the development of preventive treatments that could further be translated in the human condition.

Methods
Depending on the progress state of the projects at the time of your joining, you will learn a combination of the following methods:
– molecular biology, plasmid cloning, qPCR, Western Blotting
– viral vector design and production
– in vivo vector injections
– animal behavioral studies
– electroencephalogram (EEG) recordings in mice
– immunohistochemistry and microscopy

Contact

Marco Ledri (marco.ledri@med.lu.se)
https://portal.research.lu.se/en/organisations/epilepsy-center
https://portal.research.lu.se/en/organisations/molecular-neurophysiology-and-epilepsy-group
https://portal.research.lu.se/en/persons/marco-ledri

The long-term survival for high-risk neuroblastoma (NB) patients is lower than 50%. The occurrence of secondary tumors (metastases) fundamentally determines survival. Today, no available therapeutics successfully target metastases in NB. Common metastatic sites for NB are bone marrow and bone, followed by lymph nodes and the liver. Importantly metastatic spread patterns are different between various cancer types. Since metastatic progression is a non-random event, this strongly suggests that only tumor cells with specific capabilities can form metastases. We hypothesize that (i) these capabilities differ for metastatic tumor formation in bone marrow-, liver, and lung, and (ii) to cure children with metastatic NB, we will have to consider the metastatic sites and develop metastatic site-directed therapies. The project aims to reveal potential therapeutic target molecules on metastatic tumor cells (MTCs) by characterizing and comparing bone marrow, liver, and lung MTCs using unique NB patient-derived xenograft (PDX) models, single-cell RNA sequencing (scRNA-seq) and CRISPR /Cas9 system.

The research group is based at BMC, Lund University, within a highly collaborative and interdisciplinary research environment. It comprises four PhD students, one postdoctoral researcher, and a part-time technician as well as a clinical pathologist. The group has full access to Lund University core facilities.

Catharina Hagerling

Catharina.hagerling@med.lu.se

We invite highly motivated students to join our research group at the Clinical Research Centre in Malmö and participate in our ongoing research projects for their MSc thesis laboratory work. Our group is dedicated to studying the role of the immune system in diseases such as diabetes and cancer. The projects involve laboratory work using a variety of primary cells, cell lines, purified proteins, and patient samples. You will gain hands-on experience in planning and conducting laboratory experiments that address fundamental cellular mechanisms underlying physiological and disease processes.

We will closely guide you throughout the project. The projects include state-of-the-art methods for the investigation of cell biology, such as flow cytometry, cell metabolism (Seahorse) and confocal microscopy, protein interaction analyses using the proximity-ligation assay, and genetic manipulation employing the Cas9/CRISPR system. In addition, you will have the opportunity to learn microbiological and immunological techniques and to express and purify recombinant proteins. We use Labguru, an online laboratory notebook, to document all experiments. By participating in our research projects, you will gain valuable experience in cutting-edge research techniques, broaden your understanding of cellular mechanisms in physiology and disease, and contribute to our mission to advance knowledge in the field of immunology.

You will also become a member of a large, international research group, with many opportunities to interact with colleagues and contribute as a valued member of our team.

Below are examples of available projects:

The role of intracellular C3 and CD59 in pancreatic b-cells: Our research focuses on two important proteins found in human pancreatic islets: the central complement protein C3 and the complement inhibitor CD59. We discovered that intracellular C3 plays a key role in regulating autophagy (a process where cells clean out damaged components) and helping cells survive during stress. Now, we are investigating how C3 may influence β-cell function and how it regulates gene expression in nucleus. In addition, we are studying CD59 to understand its role in insulin secretion and b-cell metabolism and its potential impact on diabetes. By uncovering how these proteins work, we aim to reveal new insights into pancreatic β-cell physiology, allowing for a deeper understanding of diabetes.

The role of oncogene COMP in cancer: we unexpectedly found that the expression of cartilage protein COMP is associated with metastases and a poor prognosis for patients with various types of solid cancers. Additionally, COMP contributes to cancer resistance to therapy and inhibits the immune system. We aim to investigate the molecular mechanisms responsible for these novel functions of COMP, particularly those related to basic cell biology and tumor immunology. Ultimately, our long-term goal is to develop biomarkers for cancer and resistance to chemotherapy and to provide a basis for the development of novel treatments.

– King B.C., et al. (2019) Complement C3 is highly expressed in human pancreatic islets and prevents b-cell death via ATG16L1 interaction and autophagy regulation., Cell Metabolism, 29, 202-210.

– Golec E., et al. (2022) Alternative splicing encodes novel intracellular CD59 isoforms that mediate insulin secretion and are downregulated in diabetic islets., PNAS, 119, e2120083119.

– Papadakos et al.(2019) Cartilage Oligomeric Matrix Protein initiates cancer stem cells through activation of Jagged1-Notch3 signaling., Matrix Biology, 81, 107-121.

Start date is flexible. More information about our research and us can be found on our homepage: https://www.protein-chemistry.lu.se

If you are interested, please contact prof. Anna Blom, Dept of Translational Medicine, anna.blom@med.lu.se

Project information:
Recombinant adeno-associated virus (rAAV) vectors are among the most promising platforms for gene therapy, but their performance depends strongly on how the AAV genome is designed. Small changes in genomic architecture can influence expression levels, stability, packaging efficiency, and overall functionality—factors that directly impact therapeutic potential.
In this project, you will investigate how specific genome modifications affect rAAV vector performance. By designing and building new constructs and evaluating them in cell-based assays, you will contribute to the development of next-generation AAV tools with improved functionality for future gene therapy applications.

Objectives:
This master’s level project (60 ECTS) aims to design, generate, and evaluate modified AAV genome constructs to understand how genome architecture influences vector performance. You will assess expression and stability using molecular and functional readouts and compare results across designs to identify improved configurations.

Your role:

• Design AAV genome constructs and plan cloning strategies
• Perform molecular cloning and construct assembly (plasmid design and building)
• Validate constructs using quality control methods (e.g., sequencing, restriction analysis)
• Run mammalian cell culture and transfection experiments
• Perform cell-based expression and functionality assays to evaluate construct performance
• Analyze and interpret experimental data, summarize results, and propose next-step designs

This project offers hands-on experience with real-world gene therapy development challenges, combining design thinking with experimental testing. You will work in a biotech environment where your results can directly guide improved vector development.

Required knowledge:
Basic laboratory skills and motivation to work independently are essential. Experience in molecular cloning is beneficial, and prior exposure to mammalian cell culture is a plus. A strong interest in gene therapy, synthetic biology, or biotech innovation will help you thrive in the project.

Who should apply:

• Students interested in gene therapy, vector engineering, or synthetic biology
• Curious minds who enjoy troubleshooting and optimizing biological systems
• Students who like combining lab work with data exploration and interpretation
• Prior cloning experience is helpful but not required with the right motivation

Project duration: 60 ECTS

Location:
rAAVen Therapeutics, Medicon Village, Lund

Start date:
Flexible / by agreement

What you’ll gain:

• Practical experience in cutting-edge biotech and gene therapy development
• Deep understanding of vector design principles and experimental optimization
• Insight into how startups operate in an innovation-driven environment
• Opportunities to attend talks and conferences
• Optional involvement in additional lab work depending on interest and timing
• The chance to contribute to technology with real impact in gene therapy innovation

Contact

marcus.davidsson@raaven.se

www.raaven.se