Life Sciences

<h4>"Exploring the metabolism and mixture effects of the isothiazolinone biocides BIT and OIT in PLHC-1 cells "</h4>
Abstract: The powerful antimicrobial properties of isothiazolinones make them a common preservative in both industrial and consumer products. However, methylated derivatives of isothiazolinones have been associated with concerning allergenic effects leading to stricter regulations. As a consequence, industries have turned to more lipophilic isothiazolinones, such as benzisothiazolinone (BIT) &nbsp;and octylisothiazolinone (OIT), which are less regulated. Similar effects have however been reported for exposures of BIT and OIT, highlighting the importance of expanding the knowledge about these compounds, to enforce stricter regulation and potentially controlling the isothiazolinones as a group. This study aimed to investigate the toxicodynamic and toxicokinetic responses in a fish liver cell model system, Poeciliopsis lucida hepatocellular carcinoma (PLHC-1) following exposure to BIT and OIT, alone and in mixture. Results from the ethoxyresorufin-O-deethylase (EROD) assay, revealed no significant induction of the common detoxification enzyme, CYP1A, after exposure to BIT and OIT, &nbsp;thus not indicating involvement of this enzyme in their metabolism. Analysis of cultured exposure media in high performance liquid chromatography (HPLC) demonstrated cellular biotransformation of BIT into a more polar metabolite. A rapid cellular uptake of OIT was observed, however no potential OIT metabolite could be detected, neither extracellularly nor intracellularly. A cytotoxic assessment was also conducted on exposed PLHC-1 cells investigating the mitochondrial activity and membrane integrity, common markers for cellular viability. Significant toxic effects were observed on both markers after exposure to 10 µM OIT, while no effect was observed for the same concentration of BIT. However, co-exposure to these concentrations of OIT and BIT, displayed an even greater toxicity, indicating a synergistic mixture effect between the two. While this study provides valuable insights into the toxicodynamic and toxicokinetic profiles of BIT and OIT, highlighting the importance of considering mixture effects in assessing their potential health and environmental impacts, additional research is needed to fully understand their specific metabolic pathways and interaction mechanisms, to assess their long-term exposure effects.
 Examiner: Nathalie Scheers Supervisors: Malin Celander (Göteborgs universitet) &nbsp; Opponent: Johannes Panagiotidis &nbsp; Date and time: 24 May 2024, 10.30-11.30 Location: <a href="https://maps.chalmers.se/#61393995-42d3-4b0c-ba68-1fa7b4afe3c1" title="KA" data-anchor="#61393995-42d3-4b0c-ba68-1fa7b4afe3c1">KA</a>

<h4>"Using Bioluminescence Resonance Energy Transfer (BRET) Methodology to Investigate HCAR1 Signal Transduction"</h4>
 Examiner: Mikael Molin Supervisors: Simon Lind &nbsp; Opponent: Elisabeth Norberg &nbsp; Date and time: 24 May 2024, 13.15-14.15 Location:&nbsp;<a href="https://maps.chalmers.se/#77a73d20-5534-11e9-8dd5-9d5420a8a18d" title="Utsikten" data-anchor="#77a73d20-5534-11e9-8dd5-9d5420a8a18d">LIFE 7033 Utsikten</a>

<h4>"Development of a 3-D static wound model: Characterization and investigation of different stresses using Staphylococcus aureus wound isolates"</h4>
Abstract: Wounds have represented a big issue for centuries and a high cost to the health care system worldwide in recent years. Wound care, even though it is one of the biggest disciplines within medicine, has still several challenges to face. One of them: monitoring the wound healing process. Lately, multiple solutions have been developed enabling sensors using pH or temperature as sensing variables, but conventional methods are still on top. In this thesis, based on in vitro wound models, the aim was to find new biomarkers to be applied in monitoring the wound healing process. The thesis had two parts: the development of this model and the study of different stresses over the built model. The search of these biomarkers was decided to be done using omics techniques. After screening the biofilm formation capability and behaviour of seven wound isolates of S. aureus, a 3-D collagen-based wound model was implemented. The model was characterized by evaluating the bacterial growth on it at different time-points and through different microscopy techniques. Over this model, two different stresses were tested: iron starvation and oxidative stress. 2,2bipyridine and Chelex® 100 were used to induce iron starvation. The effect of 2,2bipyridine was visible evaluating the bacterial growth in E. coli (ATCC 25992), but only significant in S. aureus (ATCC 6538) when using the highest concentration. To induce oxidative stress, hydrogen peroxide (H2O2) was added over the model. The effect in bacterial growth in S. aureus (USA300 TCH-1516) was only visible at the highest concentration. Based on these results, the study of different stresses in S. aureus based on bacterial growth is not recommended due to the high adaptability seen in S. aureus. By including the measurement of new variables like pH, iron concentration or H2O2, the different scenarios of stress could be strengthened, together with the study of gene expression. Furthermore, adding specific genes related to each of the stresses in the gene expression study, these stresses could fit better a clinically relevant scenario.
Examiner: Ivan Mijakovic Supervisors: Shadi Rahimi, Leonarda Acha Alarcón, Erik Gerner &nbsp; Opponent: Sara Bauer &nbsp; Date and time: 27 May 2024, 10.00-11.00 Location: Seminar room 3039, <a href="https://maps.chalmers.se/#f20b23bb-5c36-4aad-be75-5d9d0b90e108" title="SysBio" data-anchor="#f20b23bb-5c36-4aad-be75-5d9d0b90e108">SysBio-floor 3</a>

<h4>"Machine learning for PROTACs: Predicting protein- and molecular structures"</h4>
Abstract: PROteolysis TArgeting Chimeras (PROTACs) are molecules that induce the degradation of targeted proteins and show potential as treatments for a range of diseases, including (but not limited to) neurodegenerative diseases, inflammatory diseases, cancers, and viral infections. However, PROTACs are challenging to develop due to their novel and complex mechanism of action, and current computational methods are unsuitable for studying PROTACs. This thesis investigates and evaluates the capacity of a machine learning tool, AlphaFold, for predicting PROTAC-protein structures. Furthermore, it presents the development of a novel machine learning tool that utilizes graph neural networks to identify molecular substructures of PROTACs. Accurate predictions of these structures would be useful in the design and development of new PROTACs, potentially shortening the time to discovery and consequently saving lives.
Examiner: Pernilla Wittung-Stafshede Supervisors: Rocío Mercado, Eva Nittinger (AstraZeneca), Christian Tyrchan (AstraZeneca) &nbsp; Opponent: Leo Andrekson
Date and time: 27 May 2024, 13.30-14.30 Location: <a href="https://maps.chalmers.se/#4749f4f0-8358-11e8-8cea-65be8f2c646c" title="GIGA" data-anchor="#4749f4f0-8358-11e8-8cea-65be8f2c646c">GIGA</a>
Online: <a href="https://chalmers.zoom.us/j/67678727142" title="Zoom link">Zoom</a> (Password: 90054)

<h4>"Learning meaningful representations of cells"</h4>
Abstract: Batch effects are a significant concern in single-cell RNA sequencing (scRNA-Seq) data analysis, where variations in the data can be attributed to factors unrelated to cell types. This can make downstream analysis a challenging task. In this study, a neural network model is designed utilizing contrastive learning and a novel loss function for creating an generalizable embedding space from scRNA-Seq data. When benchmarked against multiple established methods on scRNA-Seq integration, the model outperformed existing methods on creating a generalizable embedding space on multiple datasets. A downstream application that was investigated for the embedding space was cell type annotation. When compared against multiple well established cell type classifiers the model in this study displayed a performance competitive with top performing methods across multiple metrics, such as accuracy, balanced accuracy and F1 score. These findings motivates the meaningfulness contained within the generated embedding space by the model, highlighting its potential applications.
Examiner: Johan Bengtsson-Palme Supervisor: Rocío Mercado   Opponent: Anders Källberg   Date and time: 27 May 2024, 14.45-15.45 Location: <a href="https://maps.chalmers.se/#4749f4f0-8358-11e8-8cea-65be8f2c646c" title="GIGA" data-anchor="#4749f4f0-8358-11e8-8cea-65be8f2c646c">GIGA</a>

<h4>"Identifying potential interacting partners of aqua-porin 4 via a high-throughput screening method of human brain cDNA."</h4>
Examiner: Cecilia Geijer Supervisor: Kristina Hedfalk
Opponent: Oskar Blomqvist and Aline Carvalho Nejstgaard
 Date and time: 30 May 2024, 15.00-16.00 Location: <a href="https://maps.chalmers.se/#77a73d20-5534-11e9-8dd5-9d5420a8a18d" title="Utsikten" data-anchor="#77a73d20-5534-11e9-8dd5-9d5420a8a18d">LIFE 7033 Utsikten</a>

<h4>"Investigation of a secreted tannase from an unstudied acidophilic fungus: Biochemical characterization and insights into tannin-protein precipitation"</h4>
Examiner: Johan Larsbrink Supervisor: Tom Coleman
Opponent: Aleksandra Zagorska
 Date and time: 4 June 2024, 09.00-10.00 Location: <a href="https://maps.chalmers.se/#77a73d20-5534-11e9-8dd5-9d5420a8a18d" title="Utsikten" data-anchor="#77a73d20-5534-11e9-8dd5-9d5420a8a18d">LIFE 7033 Utsikten</a>

<h4>"Unraveling the role of myeloid-derived reactive oxygen species on the epithelial-to-mesenchymal transition in metastasizing cancer"</h4>
Abstract: The epithelial-to-mesenchymal transition (EMT) allows epithelial cells in primary cancer tumors to adopt a more mesenchymal morphology, thus facilitating metastasis. This process is influenced by a multitude of transcription factors and pathways, including the p53 and NF-κB signaling pathways. Myeloid cells in the tumor microenvironment produce reactive oxygen species (ROS) via the NOX2 enzyme, and while inflammation previously has been linked to EMT, the role of myeloid-derived ROS remains unknown.
The long-term aim of this thesis was to understand the intracellular pathways connecting myeloid-derived ROS and EMT in breast cancer. To this end, breast cancer cell lines of varying invasiveness were treated with H2O2, a common ROS, together with different pathway activators/inhibitors. Differences in EMT-related genes and proteins were measured using quantitative PCR and western blot, respectively. It was observed that the SNAI family of EMT transcription factors was induced by the redox regulator Nrf2, while ROS-induced SERPINE1 was regulated by p53. SERPINE1 encodes plasminogen activator inhibitor-1 (PAI-1), a biomarker in several cancers that has also been linked to EMT and inflammation. The results were validated using CRISPR-Cas9 mediated knockout of the TP53 gene. In addition, bioinformatic and in silico analyses of publicly available datasets corroborated these results.
The links between H2O2 and EMT in breast cancer implied by the results of this thesis show potential targets for limiting EMT in breast cancer. Further studies are necessary to fully understand the involved mechanisms and their regulation.
 Examiner: Anna Karlsson-Bengtsson Supervisor: Anna Martner &amp; Mustafa Kaya
Opponent: Elin Karlsson
 Date and time: 5 June 2024, 13.15-14.45 Location: <a href="https://maps.chalmers.se/#4749f4f0-8358-11e8-8cea-65be8f2c646c" title="GIGA" data-anchor="#4749f4f0-8358-11e8-8cea-65be8f2c646c">GIGA</a>

<h4>"Patient-specific analysis of ctDNA as a biomarker for childhood Acute Lymphoblastic Leukemia"</h4>
Examiner: Annikka Polster Supervisors: Fani Pujol Calderón &amp; Martin Dalin
Opponent: Anna Andersson
 Date and time: 5 June 2024, 14.00-15.00 Location: <a href="https://maps.chalmers.se/#77a73d20-5534-11e9-8dd5-9d5420a8a18d" title="Utsikten" data-anchor="#77a73d20-5534-11e9-8dd5-9d5420a8a18d">LIFE 7033 Utsikten</a>

<h4>"Myeloid Derived Suppressor Cells in Common Variable Immunodeficiency"</h4>
Examiner: Annikka Polster Supervisor: Jesper Waldenström
Opponent: Emilia Gvozdenovic
 Date and time: 12 June 2024, 11.00-12.00 Location: <a href="https://maps.chalmers.se/#77a73d20-5534-11e9-8dd5-9d5420a8a18d" title="Utsikten" data-anchor="#77a73d20-5534-11e9-8dd5-9d5420a8a18d">LIFE 7033 Utsikten</a>

<h4>"Studying interactions of complex lipid vesicles with cell membrane mimics using neutron techniques"</h4>
 Examiner: Fredrik Höök Supervisors: Margaret Holme &nbsp; Opponent: Nastaran Fallah Randjbar &nbsp; Date and time: 12 June 2024, 13.00-14.00 Location: <a href="https://maps.chalmers.se/#e3838355-3672-4a2f-8615-15e94a32dd11" title="10:an" data-anchor="#e3838355-3672-4a2f-8615-15e94a32dd11">"10:an"</a>

<h4>"Systemic inflammation in cariiovascular, renal, and metabolic diseases: Monitoring infiltration and interplay of monocytes with cardiac and kidney models on a microfluidic device."</h4>
Examiner: Annikka Polster Supervisor: Liisa Vilén (AstraZeneca)
Opponent: Emma Frisk
 Date and time: 12 June 2024, 13.30-15.30 Location: <a href="https://maps.chalmers.se/#77a73d20-5534-11e9-8dd5-9d5420a8a18d" title="Utsikten" data-anchor="#77a73d20-5534-11e9-8dd5-9d5420a8a18d">LIFE 7033 Utsikten</a>

<h4>"Non-equilibrium stabilisation of proteins by chaperones"</h4>
Examiner: Pernilla Wittung-Stafshede Supervisor: Paolo De Los Rios, Laboratoire de Biophysique Statistique (EPFL) &nbsp; Opponent: Wilma Franssila &nbsp; Date and time: 14 June 2024, 11.00-12.00 Location: <a href="https://maps.chalmers.se/#4749f4f0-8358-11e8-8cea-65be8f2c646c" title="GIGA" data-anchor="#4749f4f0-8358-11e8-8cea-65be8f2c646c">GIGA</a>

<h4>"DNA Microscopy: Establishing an immuno protocol"</h4>
Examiner: Fredrik Westerlund Supervisor: Björn Högberg, Karolinska institutet
Opponent: Maria Li López Bautista
 Date and time: 14 June 2024, 14.30-15.30 Location: <a href="https://maps.chalmers.se/#24d8b7be-1f59-4388-be28-a07861b429b2" title="PJ-salen" data-anchor="#24d8b7be-1f59-4388-be28-a07861b429b2">PJ hall</a>

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Presentation of master thesis

Master thesis presentations at Life Sciences

24 May 2024

10.30-11.30: Aline Carvalho Nejstgaard & Oskar Blomqvist, MPBIO

13.15-14.15: Emilia Gvozdenovic, MPBIO

27 May 2024

10.00-11.00: José Manuel Outomuro Ruiz, MPBME

13.30-14.30: Anders Källberg, MPBIO

14.45-15.45: Leo Andrekson, MPBIO

30 May 2024

15.00-16.00: Johannes Panagiotidis, MPBIO

4 June 2024

09.00-10.00: David Sandberg, MPBIO

5 June 2024

13.15-14.45: Olivia Johnsson, MPBIO

14.00-15.00: Wilma Franssila, MPBIO

12 June 2024

11.00-12.00: Elisabeth Norberg, MPBIO

13.00-14.00: Eleftheria Kosta, MPPHS

14.00-15.00: Thien Nguyen, MPBIO

14 June 2024

11.00-12.00: Maria Li López Bautista, MPCAS

14.30-15.30: Anna Andersson, MPBIO