Bark beetle outbreaks represent a threat to forests worldwide. Under normal circumstances, they colonize dead or low vigour trees, which promotes nutrient cycling in the ecosystem. However, in large numbers they are capable of colonizing healthy trees, using aggregation pheromones to coordinate these attacks. It has been proven that using pheromone baits as a control strategy to interfere with bark beetle behaviour is effective. Similarly, predators of these beetles are attracted by the presence of the beetles’ pheromones.
As several of these pheromones share the same C5 building block molecules as plant secondary metabolism, in the Van Aken Lab, we have engineered different metabolic pathways to produce insect pheromones from plant metabolism. Having plants producing insect pheromones opens the possibility for using them as natural dispensers of pheromones or as a biofactory for later extraction. Currently in this project, we are engineering alternative enzymes for the current pathways and new cloning strategies for improving the production of these pheromones, as well as new pathways to produce different pheromones.
In this project, we will use several cloning techniques such as Multisite Gateway cloning, Golden Gate cloning and Gibson assembly. We will work with the model organism Arabidopsis thaliana, as well as N. benthamiana and the oilseed crop Camelina sativa. We will use expression analysis via qPCR and GC/MS to evaluate plant metabolite production.
For this project, it is expected to have a student with an interest in plants and molecular biology, as well as biotechnological applications. The start date is flexible, as well as the duration of the project. If you are interested, please contact Olivier Van Aken (olivier.van_aken@biol.lu.se) for more information.
Precision gene therapy for epilepsy
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) charachterise 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.
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
Babesia divergens Genomics
Human babesiosis in Europe is mainly caused by Babesia divergens, which is also a zoonosis, but there is very little known about this important parasite. We have isolated, cultured and sequenced two new isolates of B. divergens. A student in this project is required to carry out a comprehensive genomic comparison of these isolates to identify unique gene duplication events, variations, evolution etc. The candidate is also expected to determine preferential expression of genes of interest using available RNA-seq data. Bioinformatics tools such blast, orthofinder, funAnnotate, baseSpace and others will be used so some experience using UNIX, python and R is an advantage.
This project will be supervised by Muyideen Tijani in Kristina Persson’s group/lab
Contact: muyideen_kolapo.tijani@med.lu.se
Characterization of anti-Spike IgA monomers and dimers
Master project proposal (60 credits)
When a human being is infected by a pathogen such as Sars-CoV-2, antibody production is triggered. The antibodies or so-called immunoglobulins (Ig) label the pathogen as “alien” thus guiding the immune system to react against the intruder. There are several important antibody-mediated effector functions such as
• phagocytosis (ADCP)
• cellular cytotoxicity (ADCC)
• NETosis
Even though there are five distinct classes of immunoglobulins, research’s main focus has been on IgGs while other classes remain understudied.
Our lab has started to venture into IgA research and successfully produced human monomeric IgA monoclonal antibodies against Sars-CoV-2’s spike protein. We would now like to produce dimers and characterize the abovementioned functions. The antibodies will be produced by a human cell line and purified from the supernatant with the help of FPLC. We then plan to utilize Flow cytometry, microscopy and set up biochemical assays to study the differences between IgA monomers and dimers.
Contact:
Quantitative Immunobiology Lab www.nordenfeltlab.com
pontus.nordenfelt@med.lu.se and berit.olofsson@med.lu.se
Unlocking the Mysteries of the Immune System: new Roles of complement proteins in Diabetes and Cancer.
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.
Our experienced group members 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 microbiologic and immunologic 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.
Below are examples of available projects:
The role of intracellular C3 and CD59 in pancreatic β-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 contribute to islet inflammation. In addition, we are studying CD59 to understand its role in insulin secretion and β-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 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 -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
Will perennial crops improve agricultural nutrient use efficiency via rhizosphere nitrogen mining?
Nitrogen availability is a key factor governing plant growth and soil fertility, and maintaining agricultural productivity. In agroecosystems, crops form the nexus for nutrient cycling, fueling the activity and characterising the composition of soil microbial communities. Annual and perennial crop management results in fundamentally different rhizospheres. Perennial crops form larger root systems that progressively develop over years or even decades and result in more carbon input into the soil, more complex structures of roots and rhizosphere deposits, and larger root columns. Rhizospheres create microbial habitats rich in resources and fuelling microbial communities with rhizosphere C, which often triggers microbial mining of nutrients from organic matter, a phenomenon known as the “rhizosphere priming effect” (RPE). As such, perennial agriculture likely leads to improved nutrient provisioning to the plant via aboveground-belowground interactions. However, to date, these are theoretical predictions and remain unexplored by experimentation. Thus, it still remains unclear whether perennial crops consistently stimulate microbial nitrogen mining and how this varies along depths in agricultural soils. This is the target of the proposed project.
Supervisors: Xiaojing Yang & Johannes Rousk
https://portal.research.lu.se/en/persons/xiaojing-yang
https://portal.research.lu.se/en/persons/johannes-rousk
Objectives
This project seeks to evaluate the extent to which perennial crops can stimulate nitrogen mining by soil microorganisms and identify the underlying drivers of this process. Specifically, we will draw on the SAFE (Swedish Agricultural Field Experiment) site in Löntorp to quantify microbial nitrogen mining activity in soils under perennial crop cultivation compared to annual crops. We will assess the role of root input in stimulating microbial nitrogen mining and examine how soil conditions (e.g., organic matter content, nitrogen availability) and crop traits (e.g., root biomass) influence microbial nitrogen mining. The study can involve both controlled laboratory experiments, greenhouse experiments, and field studies in agroecosystems dominated by perennial crops. The project is open to adjustments according to your interest in the topic, with the possibility of matching your research interests
Methodology
- Determine bacterial and fungal growth rates by isotope tracing.
- Measure soil respiration rates using gas chromatography.
- Tracking rhizosphere carbon (13C) into CO2 with online ring-down spectroscopy.
- Determine soil characteristics including soil moisture, C, N, pH, organic matter etc.
- Characterize microbial community composition by PLFA method.
- Collect and analyze root biomass from crops to identify carbon substrates that stimulate microbial activity.
- 15N pool-dilution method to estimate gross N mineralization rates
Skills and Techniques Acquired
- Experimental Design: Learn how to design and implement experiments to assess soil-plant-microbe interactions.
- Field and Laboratory Skills: Develop proficiency in isotope tracing, soil respiration measurement, and microbial community analysis.
- Data Analysis and Interpretation: Gain expertise in statistical analysis of environmental data and interpretation of patterns in nitrogen cycling and microbial activity.
- Critical Literature Review: Learn how to identify and synthesize relevant scientific literature on rhizosphere processes, nitrogen cycling, and soil-microbe interactions.
- Problem-Solving: Build problem-solving skills by troubleshooting challenges in both field and laboratory experiments.
Application Process
If you are interested, please contact: Xiaojing Yang xiaojing.yang@biol.lu.se and/or Johannes Rousk johannes.rousk@biol.lu.se
Epigenetic control of transposons in human brain development and degeneration (wet or dry lab)
Epigenetic control of transposons in human brain development and degeneration (wet or dry lab)
Molecular neuroscience has largely focused on the functions of protein-coding genes, which account for less than 2% of our DNA. Repetitive elements – including viral-like sequences called transposons – comprise more than half the human genome, but limitations in sequencing technologies and other molecular tools have left many repeats overlooked – so-called ‘genomic dark matter’. This is an important mechanistic blind spot: repeats are dynamic stretches of DNA that can mobilise or duplicate, and impact transcriptional programs. Repeats are the main source of individual genetic variation. When their dynamics are not controlled, repeats cause severe neurological disorders.
In the Lab of Epigenetics and Chromatin Dynamics (https://www.stemcellcenter.lu.se/research-groups/douse) we are interested in how this genomic dark matter is controlled by epigenetic mechanisms during human brain development and degeneration. We have a particular focus on how different protein complexes package repetitive DNA into chromatin, and how chromatin influences transcriptional dynamics. We combine chromatin biochemistry with functional (epi)genomics in human (neural) stem cell models.
We have multiple projects running in this area, based at BMC A11, and space for 1-2 students. The project would start in the autumn term but we are open to later start dates e.g. if there are additional courses that the student would like to take to prepare.
We are open to designing thesis projects that are wet-lab-only or dry-lab only, or a combination thereof. For the latter, it would be necessary that you have at least some knowledge of how to run basic operations from a command line. If you would like a dry-lab only project, we will prioritise students from the Bioinformatics Masters programme.
If you have any questions you are welcome to email me (Chris) directly at christopher.douse@med.lu.se – please include a brief description of why you’re interested and attach a CV, grade transcript (if available) and details of 1-2 previous supervisors or mentors who could provide a reference.
Please be aware that we would like to have the student(s) lined up well in advance of the summer break 2025. If you are interested in starting the project earlier or during the summer, we can discuss that.
Decoding the Impact of Early Systemic Inflammation on Beta-Amyloid Seeding
Alzheimer´s disease (AD) is a neurodegenerative disease and most common form of dementia. It is characterized by neuronal loss, extracellular amyloid b (Ab) plaques and intraneuronal deposits of neurofibrillary tangles (NFTs)(Selkoe, 2003). AD pathology also manifests reactive gliosis that reflects the activation of microglia and astrocytes. Besides above, myelin degeneration has been increasingly proposed as a key contributor to AD. Microglia are resident immune cells in the central nervous system (CNS). They play essential roles during development by modulating brain homeostasis, neuronal circuits and synaptic pruning(Schafer et al., 2012). In brain diseases, microglia are responsible for inflammatory responses, including phagocytosis and the secretion of soluble factors, such as cytokines, that contribute to immune responses and tissue repair. In the context of AD, activated microglia can reduce Ab aggregation by increasing its phagocytosis, clearance and degradation(Frautschy et al., 1998). Microglia have a long lifespan(Réu et al., 2017), which gives them the capacity to retain their inflammatory past, potentially leading to long-lasting effects. Although inflammation in the body is intended to be protective, an aggressive inflammatory reaction can lead to or contribute to pathological conditions(Heneka et al., 2001). Increasing evidence and my recent study(Yang et al., 2023) have shown that microglia primed with systemic infections had contradictory responses in AD animal models (Tejera et al., 2019; Wendeln et al., 2018). These studies manifest diverse microglia profiles and their impact on Ab accumulation depends on the stimulation and the duration of exposure. Moreover, other cell types, such as astrocytes and oligodendrocytes, may also play roles in AD progression.
The research project aims to identify distinct phenotypes of neurons and one glial cell type (microglia, astrocytes, and oligodendrocytes) through single-cell RNA sequencing method. The objective is to investigate how early-life inflammation influences their transcriptomic and proteomic alterations, with the ultimate goal of targeting specific pathways that modulate neuron-glia interactions. Additionally, preclinical findings will be validated using data from Alzheimer’s disease (AD) patient cohorts at the project’s conclusion.
Supervisor and contact: Yiyi Yang, yiyi.yang@med.lu.se
Affiliation: Experimental neuroinflammation laboratory, Department of Experimental Medical Sciences (EMV), Faculty of Medicine.
Bachelor/Master projects in artificial intelligence and data science for medicine, life and environmental science
The Cell Death, Lysosomes and Artificial Intelligence Group at the Faculty of Medicine at Lund University in Sweden has open positions for Bachelor/Master theses and short research projects in the following topics:
- Natural language processing with LLMs for information extraction from Swedish electronic health records (patient journals)
- Natural language processing with LLMs for information extraction from scientific literature in medicine, life and environmental science
- Database mining in medicine, life and environmental science
- Knowledge graphs in medicine, life and environmental science
- High-content microscopy analysis with computer vision deep learning models
- Interactive data visualization/visual analytics
In all projects you can gain experience in using high-performance computing resources and in applying best practices for reproducible software development and data analysis, agile project management and ethical and sustainable data science. You will also receive career mentoring and can build valuable connections within a vibrant interdisciplinary and intercultural research community, which spans across academia, industry and public sector.
We host students with an educational background from a variety of fields including but not limited to: computer science, data science, mathematics, biotechnology, biomedicine, biology, medicine.
If you are interested in Postdoctoral or PhD projects, do not hesitate to get in touch as well.
Supervisor info:
Sonja Aits
Can plants sense when they are being touched?
During evolution, plants have acquired systems enabling them to adapt to adverse environmental conditions, including responses to mechanical signals or ‘touching’. Plants use such mechanical cues to detect e.g. herbivores, wind, neighbouring plants or to find supports to climb on. The plant response to biotic and abiotic stress has been studied for many years, but the molecular mechanism controlling touch-signalling in plants is not well understood. Plants subjected to regular touching show reduced growth and development, called ‘thigmomorphogenesis’. On the other hand, the plants can become more resistant to insect pests and pathogens.
Interestingly, many genes are induced at the mRNA- and protein level within a few minutes after being touched. Recently, our lab found that touch signalling is controlled by multiple complementary signalling pathways. In the proposed work we will study candidate components of the early touch-signalling cascade such as mitogen-activated protein kinases (MAPKs) and plasma-membrane Ca2+ channels, as we suspect that they play a crucial role in the early touch-signalling cascade. We will use genetic tools to knock out genes and study the response of these mutants to touch stimulation in comparison to WT with regards to gene expression, phosphorylation cascades and alteration in growth and development. As the touch response is also rapidly switched off after 30 minutes, we are exploring the mechanism that in timely manner control mRNA degradation. The student will learn a wide range of molecular and physiological techniques.
If you are interested, please contact Olivier Van Aken (olivier.van_aken@biol.lu.se) for more information.
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