Animal Research at the IIMCB 

Participation of different animals in scientific research at the IIMCB:

Most common procedures using animals:

1. Tissue collection – animals are not subjected to any procedures during their lifetime. They are killed and the isolated tissues are then used, for example, to derive cell lines, or for molecular studies for further detailed research.

2. Experiments using animals; most common procedures using animals include:

a) Hormonal stimulation – administration of two injections containing hormones to stimulate ovulation. This procedure is analogous to preparing women for egg cell retrieval in in vitro procedures (although the number of injections is much fewer). The procedure allows us to obtain a large number of embryos, which can then be genetically modified.

b) Vasectomy – a surgical procedure performed under general anaesthesia and with intra – and postoperative pain protection. Vasectomy is used to obtain infertile males - they mate with females to “prepare” them to receive modified embryos via embryo transfer. Embryo transfer without prior preparation of females by mating with infertile males (not producing sperm, but sexually capable) is ineffective.

c) Embryo transfer – a surgical procedure involving the transfer of embryos into the fallopian tubes of recipient females. The operation is performed using a microscope, under general anesthesia, with intra- and postoperative pain protection.

d) Breeding mice with potentially harmful characteristics (phenotypes) – after developing a new line of genetically modified mice, all are observed to check if the changes have negatively affected their welfare.

e) Intramuscular injection – analogous to the methods used in humans for administering drugs and vaccines.

f)  Sensory-motor behavioural tests – this test is used to determine the overall level of activity and exploratory habits in rodent models of central nervous system disorders. The animal is placed in an arena (round/square box) and allowed to move freely for 10 minutes while being recorded by a camera. The video material is then analysed by an automated tracking system. The following parameters are considered: distance travelled, speed, and time spent in previously defined zones. This simple test is useful in assessing the impact of applied therapies on overall activity.

Ongoing Research:

mRNA (A type of RNA that carries genetic information)

1. Studying the stability and effectiveness of mRNA vaccines in various tissues. Results will help the design of targeted vaccines for specific organs.

2. Developing technology to enhance the stability and efficient replication of synthetic mRNA introduced into cells, aiming to create new anti-cancer vaccines and immunotherapeutic solutions.

3. Investigating the efficiency of delivering nanoparticles containing mRNA to different types of cells: improving therapeutic mRNA technology to develop anti-cancer mRNA vaccines.

4. Examining the mRNA release process (enclosed in lipid nanoparticles) from endosomal vesicles (responsible for transporting substances from the environment into the cell) into the cytoplasm. It is estimated that only a few to several percent of the mRNA delivered to the cell is released into the cytoplasm. Understanding this process may help increase the efficiency of therapeutic mRNA vaccines.

5. We are studying how the mouse body processes mRNA-based drugs in the absence of specific enzymes responsible for their degradation in selected tissues. The goal is to build a foundation for creating precise mRNA therapies that target specific organs.

Mutations in Genes Causing Diseases

1. Studying the effects of mutations in the mitochondrial genome across different tissues in mice. In the human population, mitochondrial disorders affect 1 in 5,000 people, causing serious nervous system and musculoskeletal symptoms for which there is currently no effective treatment available.

2. Creating a line of mice that lack a gene encoding a protein, whose inhibitor (blocking substance) may become a new drug in breast cancer treatment.

3. Researching the effectiveness of melanoma anti-cancer treatment – a dangerous malignant skin tumour detected in about 110,000 patients annually.

4. We are studying zebrafish with a genetic mutation that causes behaviors similar to autism. These include changes in social interaction, response to new stimuli, and activity of genes involved in brain development.

Brain Research (Depression)

1. An investigation of the brain of animals to see if disturbing the activity of certain selected genes leads to the same changes as those obtained in cellular studies. Checking whether these changes will affect behaviours typical of depression (e.g., increased level of helplessness) and weaken their ability to think effectively (e.g., during learning).

2. Testing in animals the antidepressant potential of 21 substances selected based on specific pharmacological characteristics. If the results are positive, collaboration with clinicians will begin to develop a pilot clinical trial. Searching for new antidepressant drugs is necessary as currently available therapies are only effective in 50% of cases, and many individuals do not respond to subsequent treatment attempts (treatment-resistant depression).

Immune System Response Research

1. Analysing the immune system response (innate immunity) to modified RNA molecules representing both viral RNA and host RNA (mice). The findings of this research will help to understand how best to prevent and treat serious viral and autoimmune diseases.

2. Studying the effects of inflammation caused by bacterial endotoxin (LPS) in mice with iron deficiency to understand the development of anaemia during infections and inflammatory diseases.

Gut Microbiota and Liver Function 

1. We are investigating how gut bacteria (microbiota) affect liver inflammation after exposure to a toxic substance found in the death cap mushroom. We are also examining how this toxin impacts liver cells and exploring ways to stop disease progression. 

2. We study how liver cirrhosis affects gut function to discover new treatment strategies.

3. We are analyzing how the gut and liver interact during cirrhosis, focusing on the role of gut microbes in disease development and how liver damage changes the makeup and function of gut microorganisms.

Iron Balance in the Body 

1. We are studying how the body removes free hemoglobin under normal conditions and during hemolysis – breakdown process of red blood cells, which happens in many diseases.

2. We are analyzing new mechanisms that regulate iron recycling from red blood cells in mice with iron-deficient diets. The insufficiency of this element represents a global medical challenge.

Animal Models of Human Diseases

By changing certain genes in animals, we can recreate diseases seen in humans. These animal models help us understand disease mechanisms and develop better treatments.

Zebrafish – introduced mutations:

• linked to Parkinson’s disease
• causing heart defects during development
• affecting inner ear development and hearing

Mice – introduced mutations:

• causing the following diseases:
  - muscular dystrophy 
  - unknown metabolic disorders 
  - neurodevelopmental conditions 
  - autism spectrum disorder 
  - leukemia
• causing drug intolerance in leukemia treatment
• affecting the formation of blood vessels

Learn more:

Animal Research
The Importance of Animal Research
Research Guidelines
Animal Research at the IIMCB