Research

The Laboratory of Animal Models focuses on generation and analysis of animal models. Our main goal is to determine the effects of genetic modifications on cognitive functions, behaviour and metabolism. We are using conventional global transgenes as well targeted mutations by Cre/lox system or CRISPR. We are producing and analyzing the following models:

 

Current studies are focused on defining activity dependent gene expression in neurons, local synaptic plasticity, microRNA function in neurons and adipose tissue. Ultimately, all introduced genetic manipulations aim to show their influence on the behaviour and metabolism of the whole organism.

Cognitive

Our current cognitive projects:

microRNAs in synaptic plasticity

The aim of the project is to define a role of microRNAs in synaptic plasticity in neurons involved in the formation of the memory trace. We are looking for microRNAs involved in the regulation of the PI3K-Akt-mTOR pathway e.g. miR-103/107. We have recently shown that loss of all microRNAs enhances memory formation in mice (Konopka et al., 2010). To study the PI3K-Akt-mTOR pathway we are using inducible, conditional Dicer and Pten genes knock-outs.

Role of CREB in spatial memory formation

The role of CREB/CREM/ATF pathway disruption in adult neurogenesis of the ICER II overexpressing rat model (Bieganska et al., 2012), generated in our laboratory. We are trying to demonstrate that disturbed neurogenesis may play a role in behavioral strategies of rats in the Morris Water Maze test and plays a role in pattern separation paradigm.

Role of TDP-43 protein in development of neurodegenerative diseases

The aim of the project is to determine an altered composition of synaptic proteins in the TDP-43 transgenic rat model that shows enhancement in memory processing (Koza et al., 2019). TDP-43, a multifunctional RNA processing protein has been recognized as a hallmark of a range of neurodegenerative disorders.

PML nuclear protein manipulation - overexpression and knock-out models

PML is known to be an important regulator of embryonic neurogenesis, however its role in the nervous system of adult mammals remains largely unknown. In our research we would like to elucidate the role of PML protein and PML nuclear bodies in the adult mouse brain. In our project we characterize the effect of PML gene overexpression and the effect of PML gene knock-out in selected regions of the hippocampus. In both cases, we use AAV vector to deliver PML into the hippocampus. The effects of overexpression or knock-out of PML are analyzed using the IntelliCage system.

 

 

Metabolic

Our current metabolic projects:

Role of microRNAs in AgRP neurons in the development of obesity

Identity of cell subpopulation in the hypothalamus which is crucial for development of the obesity phenotype following microRNA loss in the forebrain of transgenic mutants (Vinnikov et al., 2014).

c-fos in arcuate nucleus during fasting

 

microRNAs in white and brown adipose tissue

The role of microRNAs in cells of peripheral tissues involved in metabolism e.g. adipose tissue. We are focusing on investigating microRNAs induced during calorie restriction and their impact on subsequent motivation of animals to food seeking. Additionally, we are studying a function of microRNAs in thermogenesis generated in brown adipose tissue.

Influence of different diets on mouse microbiome

We are testing four diets: standard, Western Diet, High Fat Diet and ketogenic diet in mice and their influence on the composition of the microbiome. We are also monitoring the metabolic parameters and the way brain controls amount of calories animals consume. The ultimate goal in the laboratory is to combine cognitive and metabolic projects and test mice fed different diets in advanced cognitive tests in the IntelliCage.