Biology Education

Department of Biology | Lund University

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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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Flight activity of sick birds using accelerometers and machine learning

Accelerometers allow the remote study of animal activities and thus offer a huge advantage over traditional studies based on direct human observations. Beyond simple activity, accelerometry can reveal complex behaviours, such as eating and preening. This is done using supervised machine learning methods, whereby a model is trained by annotating accelerometry data with behaviours based on direct observations of tracked birds.

The aim of the project is to build a machine learning model and apply it to study the behaviour of sick birds and to test the hypothesis that repeated exposure to low-dose infection induces infection tolerance. Tolerance is manifest as an attenuated response to infection, and birds that use bird feeders could acquire tolerance if they are exposed to repeated low doses of infections at feeders. Tolerant birds produce a weaker fever and reduced sickness behaviours. This could enable them to continue to be active and subsequently transmit infections to other birds.

Great tits, housed in aviaries at the department’s field station, will be given repeated immune challenges, and the behavioural response to infection quantified using accelerometry. The student will annotate videos of tagged great tits to identify distinct accelerometry profiles associated with different behaviours. Following this, a behaviour classification model will be built on the video training data (in R) and applied to accelerometry data collected from birds following immune challenge. The student will then examine how the frequency of different behaviours changes with increasing infection exposure. The extent to which the student gets involved in fieldwork will depend on when they start the project and/or level of interest.

Contact Hannah Watson for more details: hannah.watson@biol.lu.se

 

Suggested reading:

Yu et al. 2024. Flight activity ad effort of breeding pied flycatchers in the wild, revealed with accelerometers and machine learning. Journal of Experimental Biology, 227:jeb247606. https://doi.org/10.1242/jeb.247606

Yu et al. 2023. Accelerometer sampling requirements for animal behaviour classification and estimation for energy expenditure. Animal Biotelemetry, 11:28. https://doi.org/10.1186/s40317-023-00339-w

December 2, 2024

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Biology

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Fungal interactions and succession in dead wood

In the forest ecosystem, dead wood is a dynamic and complex ecological niche in which fungi play a central role in the decomposition of lignocellulosic components. It is known that wood saprotrophs with varied life history traits produce fruit bodies in a successional order along the decomposition process of dead wood. Pioneer species with ruderal characteristics are displaced by intermediate colonizers with higher competitive ability. At late stages of decomposition or in changing environments, tolerance to stress becomes a major determinant of colonization success, either solely or in combination with ruderal and competitive characteristics. This knowledge on fungal assembly history results mainly from fruitbody inventories, but recent culturing experiments and sequencing surveys reveal that there is more going on in dead wood than what meets the eye. Preliminary results show significant differences in mycelial growth rates and enzymatic profiles that relate to the species life-history traits as well as at which successional stage they fruit.

Objectives: In this project you will follow up on studies done at the petri dish-scale by examining microscopic interactions between fungal hyphae to study how the fungal mycelia of pioneer, intermediate and late colonizers of wood interact at the micro scale in pairwise combative experiments using microfluidic chip technology. We will score their combative capabilities as deadlock or exclusion, allowing species ranking based on their competitive hierarchy. Using microfluidic soil chip systems, we will also study how different fungal species vary in their ability to colonize new environments and handle interactions with other species in confined spaces by assessing morphological responses at the micro-scale in the fungi.

Iam looking for a master student with a keen interest in:

  • Fungi (learning about fungal interactions and physiology, culturing fungi)
  • Microbial Ecology (understanding successional dynamics in wood decomposition)
  • Microscopy (most measurements are made through microscopy in chip systems)
  • Learning new techniques (microfluidics, image analysis)
  • Behavioural ecology

This project is a collaboration with Dr Sundy Maurice at the National History Museum in Paris, but all lab work will be conducted here at Lund University in the Functional Ecology division and the master’s student will be embedded in the Soil Chip research group.

If this sounds interesting to you, or you have other ideas for a master project involving fungi, please don’t hesitate to contact me: kristin.aleklett_kadish@biol.lu.se

November 4, 2024

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Biology

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To eat or be eaten – how do interactions with soil fauna impact fungal behaviour?

There are several known cases of fungi altering insect behaviour, but few studies have turned the question around and asked the opposite: how are insects and other soil fauna affecting fungal behaviour? One aspect of fungal behaviour that has been studied in relation to soil fauna is the effects of micro-arthropod-grazing on fungal growth patterns, network connectivity and exudations.

Fungi are thought to have developed various defense strategies to protect themselves from grazing collembolan by e.g. producing repellent metabolites and crystalline spikes at the surface of their hyphae. Some fungi have even turned the tables, becoming the predators themselves, by chemically immobilizing and feeding on the collembola. However, it is still unknown what triggers the initiation of these defensive mechanisms, and further, what happens to the behaviours of the rest of the mycelia when the interaction is initiated? Do resources get re-allocated, explorative growth directed away from the attack or is mycelial interconnectedness strengthened under stress?

Objectives: In this project (45-60 cr.) you will learn how to culture fungi and study how grazing collembola impact growth rates and trigger responses in a series of fungal species, including known collembola-killers such as the ectomycorrhizal fungus Laccaria bicolor. Using microfluidic soil chip systems, we will also study how different fungal species vary in their ability to defend themselves by assessing morphological responses at the micro-scale in the fungi and mortality rates in collembola.

I am looking for a master student with a keen interest in:

  • Fungi (learning about fungi, culturing fungi)
  • Soil Ecology (understanding trophic interactions in the soil)
  • Microscopy (most measurements are made through microscopy)
  • Learning new techniques (microfluidics, image analysis)
  • Behavioural ecology

Lab work will be conducted here at Lund University in the Functional Ecology division and the master’s student will be embedded in the Soil Chip research group.

If this sounds interesting to you, or you have other ideas for a master project involving fungi, please don’t hesitate to contact me: Kristin Aleklett Kadish, kristin.aleklett_kadish@biol.lu.se

October 30, 2024

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Biology

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Plant diversity effects on soil microbial drought tolerance

The loss of plant diversity is a growing global concern, driven by changes in land-use and climate. Maintaining plant diversity is important for ecosystem functions, such as carbon storage which is regulated by soil microbial communities. Plant diversity is particularly important during more frequent and intense drought events under climate change. While it is well known that ecosystems with high plant diversity are better to maintain functional stability under drought, less is understood about how plant diversity influences soil microbial responses during drought cycles. Soil moisture is a key factor controlling soil microbial communities, and as such drought will affect their ability to regulate soil functions. Therefore, understanding how plant diversity impact soil microbial functions during drought is crucial.

Objectives
This project aims to determine how plant diversity affect soil microbial tolerance and recovery to drought. We will set up two different plant diversity and drought treatments using a greenhouse pot experiment. The experiment will represent Swedish grasslands using common grass species, including a high diversity and a low diversity grassland community. We will evaluate the microbial ability to deliver soil functions and sensitivity to drought by resolving responses of growth and respiration both during and after drought, as well as associated soil and plant characteristics. The project will focus on soil microbial communities and is open to a tailored design that matches your interest within the topic. By combining the effect of plants and microbial communities we will determine how climate change impact soil microbial communities and their processes such as CO2 in different plant treatments, along with carbon and nitrogen-use efficiencies.

Methodology

  • Determine bacterial and fungal growth rates by radioactive isotope tracing
  • Estimate plant and soil respiration using both gas chromatography and continuous fluxes
  • Estimate GPP, NPP and NEP using light and dark chamber systems
  • Learn how to assess micrometeorological assessments of soil moisture and temperature
  • Assess key plant traits, including height, biomass, root production, and nutrient contents
  • Determine soil characteristic including soil moisture, C, N, pH, organic matter etc.
  • Asses microbial community composition using 16S/ITS amplicon assessments of extracted
  • DNA, and the size and abundance of microbial groups using PLFA
  • Determine gross and net nitrogen mineralization and nitrification using 15N pool dilution

Skills and techniques acquired

  • Design and manage a greenhouse experiment with focus on grass mesocosms
  • Learn about plant traits and link them to microbial community responses
  • Assess the soil carbon budget during drought cycles
  • Developed problem-solving strategies and explore various approaches related to running a
  • greenhouse experiment
  • Statistical analysis and curve fitting to interpret patterns of microbial drought responses and
  • correlate them with other measured variables

Application process

Flexible starting date, but preferably autumn 2024
If you are interested, please contact: Sara Winterfeldt, sara.winterfeldt@biol.lu.se and/or Johannes Rousk, johannes.rousk@biol.lu.se

October 29, 2024

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Biology

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Thermal adaptation of soil microbes

Soil microbial decomposers, including bacteria and fungi, are the gatekeepers of the soil carbon cycle, determining the fraction of decomposed carbon that becomes part of their biomass or is released into the atmosphere through respiration. In the context of climate change, understanding how rising temperatures will affect these microbial communities is crucial for predicting global carbon fluxes. Elevated temperatures could either increase or decrease the amount of carbon released into the atmosphere by soil microbes.
Numerous studies have shown that soil bacteria and fungi exposed to rising temperatures in situ exhibit shifts in their growth rate temperature dependencies, with both their minimum and optimal growth temperatures moving upward in response to the warming conditions. However, these adaptations are often measured at the community level, which limits our understanding of the ecological mechanisms involved. It remains unclear whether these changes are due to shifts in community composition toward warm-adapted taxa or physiological acclimation and evolution within existing taxa—possibly through mechanisms like horizontal gene transfer.

Objectives
This project aims to elucidate the mechanisms by which soil microbial communities adapt to increasing temperatures at the species level. By comparing the thermal traits of bacterial and fungal strains isolated from artificially warmed soils, we seek to determine whether thermal adaptation results from species sorting or physiological changes within species. Bacterial and fungal populations will be isolated from both control (ambient temperature) and warmed soils. These strains will be identified using DNA barcoding, and their thermal traits will be analyzed in relation to their phylogeny. The findings will be compared with previously acquired community-level thermal trait data to assess whether community-level thermal adaptation is primarily associated with microbial species sorting or physiological adaptation, and to determine if these processes differ between bacteria and fungi.

Methodolog

  • Isolate bacteria and fungi from artificially warmed soils.
  • Identify bacterial and fungal strains using DNA barcoding techniques.
  • Measure growth rates of bacterial and fungal isolates at different temperatures.
  • Model growth rates as a function of temperature to determine thermal traits.

Skills and techniques acquired

  • Microbiology techniques for isolating and identifying microbes the molecular level.
  • Methods for axenic bacterial and fungal cultivation and phenotyping.
  • Analyzing thermal adaptation traits in relation to microbial phylogeny.
  • Advanced data analysis and visualization skills.

 Application process

October 29, 2024

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Biology

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Climate change impacts on plant microbiota

Bacteria and fungi associated with plants play critical roles in plant growth, fitness, and stress tolerance. These microbial communities inhabit the rhizosphere—the soil zone influenced by root secretions—and internal plant tissues both belowground and aboveground, collectively known as the plant microbiome. While considerable progress has been made in understanding how disturbances like pathogen outbreaks, invasive species, and pollution affect plant microbiomes, there is limited research on the impacts of climate change-associated disturbances.
In boreal and subarctic areas, ericaceous shrubs (members of the family Ericaceae) often dominate the vegetation and form specialized symbiotic relationships with ericoid mycorrhizal fungi, essential for nutrient uptake in nutrient-poor soils. Climate models predict that heatwaves will increase in frequency and intensity in these regions due to climate change. Understanding how these heat stress events affect shrub-associated microbial communities, both belowground and aboveground, is crucial, as alterations in the microbiome can influence shrub health, survival, and ecosystem dynamics.

Objectives
This project aims to understand how acute heatwaves affect microbial communities associated with three different ericaceous shrub species. We will investigate whether such climatic disturbances influence plant-associated microbial diversity and composition in both belowground and aboveground habitats, as well as plant physiology, using an artificial warming experiment at the Abisko Field Station. By combining microbial community sequencing and plant tissue biochemical characterization, we seek to determine how future climatic disturbances might affect shrub microbiomes and identify potential microbial bioindicators of these changes.

Methodology

  • Evaluate shrub root fungal colonization.
  • Determine bacterial and fungal community diversity and composition from soil and plant
    habitats, including roots and leaves.
  • Assess plant biochemical composition.

Skills and techniques acquired

  • Root staining and microscopy to assess mycorrhizal and endophytic fungal colonization.
  • Bacterial and fungal metabarcoding, including DNA extraction and amplification, to profile
    plant-associated microbial communities.
  • Bioinformatics analysis of high-throughput sequencing data to identify microbial taxa and
    assess community diversity.
  • Statistical analysis to interpret patterns in microbial communities and correlate them with
    environmental variables.

Application process

October 29, 2024

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Biology

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Mineral-associated organic matter formation

Soils are the largest organic carbon reservoir in terrestrial ecosystems, storing carbon as organic matter derived from decomposed plant, microbial, and animal residues that resist microbial decomposition. Recent research has revealed that organic molecules adsorbed onto soil mineral nanoparticles, such as iron and aluminum oxides, form the most stable and persistent pool of organic carbon in soils. However, the environmental factors driving the formation and destabilization of mineral-associated organic matter (MAOM) remain poorly understoodIn boreal and subarctic regions, climate change is causing trees and shrubs to encroach upon tundra ecosystems, leading to significant decreases in soil organic carbon stocks. While most studies have focused on the organic layers of soils—primarily composed of particulate plant residues—there is limited knowledge about how changes in vegetation types affect organic carbon stored in the mineral soil layers as MAOM.

Objectives
This project aims to understand how the progression of trees and shrubs affects MAOM processes in subarctic soils. To achieve this, we will utilize a natural ecotone from dwarf birch forest to tundra in the Swedish subarctic as our study site. By employing a new probe system, we will quantify MAOM formation and destabilization rates across this gradient. We will then compare these rates with various plant parameters (such as species composition, and tree density), soil parameters (including organic matter stocks, pH, moisture, and temperature), and microbial parameters (bacterial and fungal community diversity and composition). This project aims to identify the abiotic and biotic drivers influencing MAOM processes in subarctic mineral soils.

Methodology

  • Analyze MAOM probes to determine stabilization and destabilization rates.
  • Assess plant parameters to evaluate their influence on MAOM processes.
  • Measure soil parameters to determine their effect on MAOM processes.
  • Examine soil microbial parameters to understand their role in MAOM processes.

Skills and techniques acquired

  • Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy.
  • Stable isotope tracing using ¹³C and ¹⁵N isotopes.
  • Soil organic matter fractionation techniques.
  • Bacterial and fungal metabarcoding to determine soil microbial community composition.
  • Advanced statistical analysis and data visualization.

Application process

October 29, 2024

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Biology

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