Biology Education

Department of Biology | Lund University

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The molecular mechanism of mitochondria-to-nuclear signalling

To survive in the variable conditions of the outside environment, plants constantly need to adapt their growth and reproduction strategies. Due to climate change, plants and commercial crops will be more and more exposed to extreme weather variations, so it is very important to understand how they sense and manage different stress conditions such as flooding, drought, heat and high salinity.
Mitochondria are one of the key cellular organelles that mediate energy conversion and are thus tightly linked with the overall survival of an organism. In our lab, we are studying a molecular signalling pathway that allows communication between the mitochondria and nucleus, so-called mitochondrial ‘retrograde’ signalling. Mitochondrial ‘retrograde’ signalling is triggered by reactive oxygen species (ROS) produced by the mitochondria during stress, leading to activation of a transcription factor that is anchored in the endoplasmic reticulum (ER) membrane. The goal of the project is to identify the mechanism by which the ER-bound transcription factor is cleaved by proteases, to allow relocation to the nucleus and switching on gene expression. Furthermore, we are exploring how mitochondrial signalling actively slows down plant growth to potentially increase survival. The project will involve confocal microscopy, gene expression, proteolytic and phenotypic analysis. We are also studying the evolutionary origin of mitochondrial signalling in plants, using representatives of early plant lineages such as mosses. If you are interested, please contact olivier.van_aken@biol.lu.se!

January 21, 2025

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Molecular Biology

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Using the Swedish Cardiopulmonary Bioimage Study to predict vascular disease and cognitive dysfunction in humans

Despite advancements in prevention and treatment, cardiovascular disease remains the leading global cause of mortality and is projected to result in 20.5 million deaths by 2025. Both diabetes and aging independently elevate the risk of vascular inflammation, which contributes to atherosclerotic lesions and vascular dysfunction in organs such as the heart, kidneys, and brain. The growing prevalence of diabetes, coupled with an aging population, underscores an urgent need for innovative therapeutic approaches targeting diabetes-related vascular dysfunction. Our research focuses on the role of vascular smooth muscle cells as key regulators of vascular health.

The Swedish Cardiopulmonary Bioimage Study (SCAPIS) is a population-based research project involving 30,000 participants aged 50–64 from six Swedish hospitals. SCAPIS stands out due to its large scale and comprehensive phenotyping. It aims to advance the prevention, diagnosis, and treatment of cardiovascular and pulmonary diseases by combining advanced imaging techniques (e.g., CT, ultrasound) with extensive data collection on lifestyle, genetics, and biomarkers. By identifying new risk factors, biomarkers, and mechanisms underlying conditions like heart attacks, strokes, and COPD, SCAPIS contributes to precision medicine and early intervention strategies.

This project aims to analyze genotyping data from SCAPIS to improve predictions of diabetic vascular disease and cognitive dysfunction. The study involves using PLINK for genetic data analysis and developing machine learning algorithms to explore associations between specific genetic profiles and disease outcomes.

The research group (Molecular Vascular Physiology) is situated at BMC D12 in Lund. The project is ideal for a master student with an interest in deep learning models and polygenic risk scoring for vascular disease. We are seeking a motivated trainee to join our team in the spring of 2025. While our lab currently has limited bioinformatics expertise, we are in the process of recruiting a data analyst to support the group. Additionally, we collaborate with the research group “Artificial Intelligence and Bioinformatics in Thoracic Surgical Science” on this project.

Contact info: Sebastian.Albinsson@med.lu.se

January 14, 2025

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Bioinformatics

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How does forest management affect the soil microbial resilience to drought?

Climate change is a growing global concern and is predicted to increase the intensity and frequency of extreme weather events, such as drought. Soil microorganisms play a central role in the cycling of carbon and nutrients in forest ecosystems, being their activity highly dependent on water availability. Thus, drought imposes challenges to microbial life in soils, and it is still unknown how drought affects important microbial functions such as soil carbon storage and nutrient provision to plants. In this project we aim at studying how soil microorganisms cope with drought under different forest management practices.

Objectives
This project aims to understand how forest drought affects soil microbial resistance (ability to function in dry soil) and resilience (ability to recover after soil is rewet) to drought, and the consequences this has for the microbial contribution to C and nutrient cycling. We will set up experimental sites with rain-exclusion shelters ina forest ecosystem, and we will simulate seasonal drought along with rewetting events in situ. In addition, we will explore how different management practices (thinning, clear-cutting, residue return treatments, etc) modulate microbial responses drought and rain events. We will evaluate the microbial performance to deliver ecosystem functions and sensitivity to drought by resolving responses in growth and respiration, as well as associated soil characteristics in different management treatments. By combining the effect of drought in soil and in their microbial communities we will determine how climate change impact soil microbial communities and their processes such as CO2 emission, along with the potential for C storage in forest soils. The project is open to adjustments according to your interest within the topic, with the possibility to match your research interests.

Methodology:

  • Determine bacterial and fungal growth rates by isotope tracing
  • Estimate soil respiration using both gas chromatography and continuous soil fluxes
  • Learn how to assess micrometereological assessments of soil moisture and temperature.
  • Determine soil characteristic including soil moisture, C, N, pH, organic matter etc.
  • Assess microbial community composition

 

Skills and techniques acquired:

  • Design and manage a field experiment with focus on rain and drought simulations
  • Learn about how soil moisture and link it to microbial community responses
  • Assess the soil carbon budget during drought and rain cycles
  • Develop problem-solving strategies and explore various approaches related to running a field
    and lab experiment
  • Search and compile relevant literature within the topic
  • Data treatment and statistical analysis of environmental data to interpret patterns of
    microbial drought responses

Application process:
If you are interested, please contact: Margarida Soares margarida.soares@biol.lu.se and/or Johannes Rousk johannes.rousk@biol.lu.se

January 13, 2025

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Biology

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Visualizing codon usage in proteins

Traditionally, the choice of codons to encode amino acid sequences of proteins has been assumed to be neutral terms of fitness. We now know that synonymous substitutions that do not change amino acid identities can strongly influence the function of proteins. This is because codons affect mRNA stability, expression levels, protein folding rates, and how the protein folds as it emerges from the ribosome. We study how the choice of codons is correlated with the three-dimensional structure of proteins and the evolution of codon usage. Our work has resulted in a database where codon usage is correlated with 3D protein structure and other features. This database can be mined to identify correlations between structural features in protein, such as secondary structure, and codon usage. We also built large language models of codon sequences to understand what features control codon usage in coding sequences.

Project: We would like to develop better ways to visualize our data by creating a webpage that displays the data in our database. This includes mapping codon sequence biases onto 3D structures, visualizing codon conservation in protein families, and mapping coding usage on species phylogenetic trees.

Desired background: The candidate should have a strong interest in visualization and a solid background in Python programming.

Environment: In addition to research on codon usage, the research group (andrelab.lu.se) also does research in protein structure prediction, computational protein design, and protein evolution. The group uses a range of computational approaches (from deep learning to molecular simulation) and experiments to complement computational projects, providing a multidisciplinary environment for a thesis student to learn.

Contact: If this sounds interesting to you, contact Ingemar André, ingemar.andre@biochemistry.lu.se, for further information.

January 3, 2025

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Bioinformatics

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Acute lymphoblastic leukaemia (BCP-ALL)

“B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common childhood cancer. Despite a good prognosis, two major clinical issues remain. Firstly, about 10% of children do not respond to standard treatment, making relapsed BCP-ALL the second largest cause of pediatric mortalities in the Western world. Secondly, current chemotherapy protocols (which last several years) are incredibly harsh, directly contributing to the global death toll and causing many long-term medical complications for survivors (spanning both physical and cognitive impairments).

Through several single-cell resolution analyses, we previously demonstrated that fuelled by parallel evolution and phenotypic convergence processes, a rare population of transcriptionally uniform – deeply quiescent – but genetically variegated cells escape induction chemotherapy (Turati et al., Nat. Cancer 2021). These data suggest that a better understanding of how cell quiescence in BCP-ALL is regulated, and impacted by chemotherapy, could help guide future efforts to improve and de-escalate treatment.

During the course of this project, you will probe proliferation/quiescence potential of individual BCP-ALL cells using a newly published functional cellular barcodes system called “Watermelon” which allows simultaneous tracing of individual cells’ lineage (clonal origin), proliferative history (quiescence potential), and global transcriptional state. Depending on the project length – and your specific research interest – you might learn one or more of the following: i) how maintain and expand BCP-ALL cells in vitro using an innovative  induced pluripotent stem cells (IPS)-based BM organoid system, ii) how to generate and exploit a barcode library, and iii) how to identify and longitudinally track phenotypic changes in BCP-ALL cells exposed to treatment (via flow cytometry, microscopy and/or sequencing).

We are looking for a MSc (ideally over 20-week project) eager to learn the ropes of how wet lab works and interested in the biological questions and techniques highlighted above. Previous training/knowledge of cancer biology, as well as experience with cell culture and molecular biology are both desired but not required. The lab is located in the BMC A12 Molecular Haematology and Gene therapy unit.

If you have any questions you are welcome to email virginia.turati@med.lu.se

December 30, 2024

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Molecular Biology

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Genes that regulate immune cell formation and function in humans

Our lab works on identifying the genes that regulate immune cell formation and function in humans. For this, we have produced large datasets of paired immunophenotypic data (1500 immune cell features measured by flow cytometry) and genome-wide genotype data in thousands of individuals. The flow cytometry data is analysed by a method called “gating”, where each cell is classified into different categories according to parameters like size, complexity and surface protein expression. To automate the gating process, we have developed pattern recognition tool (AliGater). We are now looking for a student who will use AliGater and extend the tool as needed to gate a new set of samples.

This project is suitable for a for ambitious students who are comfortable with Python, ideally as a 30 credit project. You will get support from the developers of AliGater and work together with a diverse team of researchers with clinical, wet lab and bioinformatics expertise.

For more information, contact: Aitzkoa Lopez de Lapuente Portilla aitzkoa.lopez_de_lapuente_portilla@med.lu.se

December 27, 2024

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Bioinformatics

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Investigating genetic causes of neurological disorders

Our Clinical neurogenetics research group is focused on the investigation of the genetic background of a number of neurological disorders. Patients with disorders like Parkinson disease, dystonia, ataxia, hereditary causes of dementia or stroke, are examined at the Department for Neurology, Skåne University Hospital, within research studies and their potential contributing or causative genetic factors are elucidated. The aim of our research is to identify new gene mutations that cause these diseases and to understand how gene mutations affect cellular mechanisms.

At present, we can offer the following project for a bioinformatics masters student:

We performed genetic testing on 12 samples from patients with frontotemporal dementia and Whole Genome Sequencing (WGS) data from these patients are available for analysis. The overall aim of this project is to investigate the data for potential genetic variations that can cause this disorder, as for example Single Nucleotide Variants (SNVs) and Short Tandem Repeats (STRs).

Applicants:

MSc bioinformatics students with an interest in neurogenetics are very welcome to apply. Familiarity with Bash, Python and Linux is a requirement. Recommended project length is 15cr (10 weeks).

Supervisors:

Efthymia Kafantari (MSc in bioinformatics and in medical genetics), Department for Neurology, Skåne University Hospital and Clinical Neurogenetics, Lund University (primary supervisor)

Joel Wallenius (MSc in bioinformatics), Department for Neurology, Skåne University Hospital and Clinical Neurogenetics, Lund University

Andreas Puschmann (neurologist, professor), Department for Neurology, Skåne University Hospital and Clinical Neurogenetics, Lund University

Contact:

Efthymia Kafantari      efthymia.kafantari@med.lu.se

Joel Wallenius              joel.wallenius@skane.se

Andreas Puschmann   andreas.puschmann@med.lu.se

December 17, 2024

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Bioinformatics

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Deciphering and modeling cell cycle regulomes underlying tumor resistance

Remarkably few vertebrates display tumor resistance properties. This select group includes salamanders, renowned for their tumor resistance, yet the molecular mechanisms underlying this ability remain unknown. Inspecting the attributes of salamanders reveals their massive genomes, ranging from 4.5 to 43 times larger than the human genome, as a unique biological feature. The sheer volume of genetic material in salamander cells makes the task of cell division complex, in terms of replication and also energetic demands. What are the advantages associated with possessing a giant genome? Our preliminary results suggest that giant genome size has imparted pressures that shaped novel innovations in cell cycle control. These innovations may be linked to the noted tumor resistance observed in newts.

The project: Others and we have created various scRNAseq datasets from animals with various genome sizes, different tissues, and across contexts (e.g., development versus adult homeostasis). The susceptibility to cancer and requirements for cell cycle regulation vary across these contexts. This project entails generating convolutional neural networks for coexpression to define the cell cycle regulome and its plasticity across cell types, lifestage, and phylogeny. The goal is to define a core, evolutionary conserved cell cycle regulome and subnodes of this regulome that are deployed across various species, genome sizes, and cell types. Moving forward, we will embed the neural-network-derived gene regulatory network into an agent-based model (ABM) aimed at quantitating the network resilience to specific gene perturbations.

The student: Master student (preferably 60cr thesis) with experience in bash, R or python. Experience in Java and/or neural networks and deep learning is advantageous.

What to expect: You will become well versed in quality control of publicly available data, working with various non-human species datasets, data integration, and workflow management. You will learn about cell cycle biology and explore its divergences across species. Depending on progress and interest you may also delve into generating neural networks and their integration in ABMs.

If this sounds of interest, please email nicholas.leigh@med.lu.se and virginia.turati@med.lu.se with a short motivation for what interests you about this project and your CV.

December 12, 2024

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Bioinformatics

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Complex Genomes in Cancer

We use whole-genome and whole-transcriptome sequencing data from primary cancer samples to elucidate genetic subgroups of potential clinical relevance. Our next step will be to identify mutational signatures on the single-nucleotide, copy number and structural variant levels. To do so, multiple variant callers will be used, their output consolidated into a consensus list of variants per case, and then signature profilers will extract and annotate relevant mutational signatures. The project would entail setting up a pipeline that can generate variant call format (vcf) files from ready-mapped whole-genome sequencing data, match the output of multiple variant callers within each category of mutations and then apply signature extraction tools.

Contacts:

Karolin Hansén Nord PhD,  karolin.hansen_nord@med.lu.se

Associate Professor, Senior Lecturer

 

Karim H. Saba PhD

Associate Researcher

 

Division of Clinical Genetics

Department of Laboratory Medicine

Faculty of Medicine

Lund University

Web page Complex Genomes in Cancer

December 11, 2024

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Bioinformatics

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Co-option of endogenous retroviruses in human synaptic maturation

Description: Endogenous retroviruses (ERVs) are genomic remnants of retroviral infections and subsequent expansion that are present in most organisms. In the human genome ERVs occupy approximately 8% of our DNA, some of which retain enhancer and promoter sequences to drive the expression of their viral-genes. However, many of these sequences also affect the expression of other nearby genes in the host genome. Recent research suggests that ERVs have been evolutionarily selected in genomic locations where they can drive or boost the expression of immune-related genes. They can also trigger an immune response by the transcription of their viral-genes.

Aberrant ERV transcription has been observed in several neurological diseases and upon neuroinflammation. Interestingly, an ERV-derived envelope protein has been found in cerebral spinal fluid in about a third of schizophrenia patients of a large cohort, and researchers at our lab have shown that the presence of this protein in the brain impairs synaptic maturation in mice models (DOI: 10.1126/sciadv.abc0708).

To study if this is the case in human neurons and provide a potential therapeutic model, the lab has been growing neuronal cultures transcriptionally activating ERVs using a CRISPR activation system. We have, so far, validated 3 guides using induced pluripotent stem cells and are waiting for the sequencing data of the neuronal cultures experiments. 

This project represents a bioinformatic challenge given that the envelope protein identified at psychiatric patients has not been pinpointed to a specific genomic locus. We have or are in the process of creating several datasets related to this project including bulk RNAseq, single nuclei RNAseq, CUT&RUN for histone modifications and long read RNAseq. 

We are looking for: Master student (preferably but not exclusively of 60cr thesis) who feels comfortable working on the terminal (bash), scripting with R, and using git. Knowledge on workflow management (Snakemake or Nextflow) is a plus. 

You will gain experience with: workflow management, making your own pipelines and using others, working on a computing cluster, using git, using statistical models to identify differentially expressed genes between experimental conditions accounting for batch effects and other covariates, transposon biology and how to adequate your bioinformatical approaches for repetitive elements, scientific thinking, visualization, and writing. 

If you find this project interesting, send me a message to raquel.garza@med.lu.se, tell me what you find interesting about it, and a little bit about your experience and ambitions! 

December 10, 2024

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Bioinformatics

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