Szanowni Państwo,

Serdecznie zapraszamy na Seminarium Doktorantów, które odbędzie się 30 września 2022 r. o godz. 9.30 w Sali im. Konorskiego (II piętro). W programie przewidziane są 4 prezentacje:

1) Maria Kulesza

2) Aleksandra Cabaj

3) Karolina Piecyk

4) Iga Stukan

Informacje dotyczące prelegentów wraz z abstraktami znajdują się poniżej.

Seminarium odbywać się będzie w trybie hybrydowym.

Link do spotkania

https://zoom.us/j/91969499353?pwd=L2ZKbDVoZlVtN1dBcW1kU1R2TXVnUT09

1. Maria Kulesza

Laboratory of Brain Imaging

Supervisor: Dr hab. Artur Marchewka, prof. IBD

Auxiliary supervisor: Dr Marek Wypych

Title: Neural processing of emotionally charged autobiographical memories in women with major depressive disorder and borderline personality disorder

Abstract

Our past experiences and knowledge about ourselves are stored in autobiographical memory (AM). Due to their emotional and sensory details, we are able to recall and relieve them. AM is important for, e.g., proper emotion regulation and development of identity. Previous studies showed a network of brain regions involved in AM recall in healthy population, including the limbic system, prefrontal, and occipital cortices.

AM recall may be disturbed in several clinical disorders, such as major depressive disorder (MDD) and borderline personality disorder (BPD) - they recall more negative and less detailed experiences. These patients have disturbed emotion regulation and sense of self.

Here, I compared the neural processing of sad (SM) and happy memories (HM) in women with MDD, BPD, and healthy control (HC) who were asked to recall and rate the memories during an fMRI session.

The main effect of recall showed robust activations across the AM recall network. The comparison of SMs and HMs revealed greater activations within this network in SMs. Functional connectivity analysis revealed increased connectivity of the left precuneus and right occipital cortex for MDD and BPD groups taken together, compared to HC. This finding suggests that, compared to HC, MDD and BPD patients have stronger associations between visual imagery and self-referential processing during emotional AM recall.

2. Aleksandra Cabaj

Laboratory of Bioinformatics

Supervisor: Dr hab. Michał Dąbrowski, prof. IBD

Title: Modelling the impact of Hypoxia Inducible Factors binding on gene expression in human endothelial cells during hypoxia

Abstract

During hypoxia, a cellular adaptive response activates hypoxia-inducible factors (HIFs), mainly HIF-1 and HIF-2 which are activated by low tissue-oxygen levels and bind to hypoxia-response elements (HREs) in the promoters or enhancers of target genes. HIF-1 and HIF-2 regulate endothelial cell adaptation by activating gene-signaling cascades that alter energy metabolism, promote angiogenesis and cell survival. A switch from HIF-1 to HIF-2 governs the transition from acute (2-8h) to prolonged (8-16h) hypoxia, with HIF-1 dominating at 2h and HIF-2 at 8h. In previous works, we found that the higher number of HRE motifs in gene promoters correlates with an earlier activation time of those genes during hypoxia. In a recent study, we demonstrated that there was a linear dependence between the count of HRE motifs annotated to HIF-1 in the DNaseI-hypersensitive regions within a ±10kb flank of the transcription start sites and the fold change of the induction due to the silencing HIF1A at 8 h of hypoxia. To explore this further, we constructed a dynamic Ordinary Differential Equations model to assess the relationship between HIFs and HRE motifs in gene promoters on binding and its impact on target gene expression during hypoxia.

3. Karolina Piecyk

Laboratory of Imaging Tissue Structure and Function (Interdisciplinary Doctoral Studies TRI-BIO-CHEM)

Supervisor I from the Nencki Institute: Prof. dr hab. Joanna Szczepanowska

Research tutor: Dr Dominika Malińska

Supervisor II from the Faculty of Chemistry, University of Warsaw: Prof. dr hab. Paweł Kulesza

Research tutor: Dr hab. Iwona Rutkowska, prof. UW

Title: Comparison of mitochondrial function in aging primary human fibroblasts. Effect of daidzein.

Abstract

To maintain well-functioning mitochondria in adaptation process to changing cellular energy demands, mitochondria undergo remodeling through dynamics processes like biogenesis, mitophagy/autophagy and morphology of mitochondrial network. The aim of our study was to investigate how mitochondria adapt to the aging process in fibroblasts. For that we investigate functioning of mitochondria in ageing fibroblast: one line derived from higher passages (>18) and the other was induced by oxidative stress.

In the applied model we find the differences in mitochondrial membrane potenial, ROS production, and the level of Ca²⁺. Also, mitochondrial turnover and mitochondrial network morphology were changed in response to ageing. Phytoestrogen - daidzein affect mitochondrial biogenesis, mitochondrial network and mitophagy/autophagy.

We can therefore suggest that mitochondria change their function during the aging process, adapting to changed conditions. Phytoestrogen - affects the mitochondrial adaptation process in aging fibroblasts.

This study was supported by a grant 2019/35/B/NZ1/02546 from the NCN, Poland (PB), partially by Nencki Institute. Work implemented as a part of Operational Project Knowledge Education Development 2014-2020 co-financed by European Social Fund; POWER.03.02.00-00-I007/16-00

4. Iga Stukan

Laboratory of Preclinical Testing of Higher Standard

Supervisor: Prof. dr hab. Urszula Wojda

Title: Preclinical evaluation of BK124.1 as a novel anticancer chemotherapeutic.

Abstract:

The search is ongoing for new anticancer therapeutics that would overcome chemotherapy

resistance. The aim of this study was to preclinically evaluate a new dicarboximide designated

BK124.1 (C 31 H 37 ClN 2 O 4 ) as a potential anticancer drug. We determined the formulation, route of administration, dosage and pharmacokinetic profile of BK124.1 in mouse and rat model, followed by successful tumor shrinking experiment in human xenograft nude mouse. Moreover, the compound showed high cytotoxicity not only against chronic myeloid leukemia K562 cells (IC 50 =2.5 µM), but also against acute lymphoblastic leukemia MOLT-4, colorectal cancer Caco-2 (IC 50 =4.3 µM) and multiple myeloma U266 cells (IC 50 =15 µM). In K562 blasts, BK124.1 decreased the protein levels of BCR-ABL1 kinase and its downstream effectors, resulting in G2/M cell cycle arrest and apoptosis associated with FOXO3a/p21 waf1/cip1  upregulation in the nucleus. BK124.1 was also cytotoxic against particularly

chemoresistant cells: K562-MDR1 (multiple resistance type 1; IC 50  = 2.16 µM) and primary CML CD34 +  cells (IC 50  = 1.51 µM) isolated from chronic phase CML patients, including CD34 + /CD38 -  drug resistant cancer initiating stem cells. Given the advantages of BK124.1 as a potential chemotherapeutic and its unique ability to overcome BCR-ABL1 dependent and independent multidrug resistance mechanisms, future development of BK124.1 could offer a cure for CML and other cancers resistant to present drugs.