The department is focused on the research of the early embryogenesis of mammals and the change in the plasticity of the cell nucleus, which accompanies the process of differentiation and dedifferentiation. These processes are accompanied by a significant change in the morphology of the nuclei and epigenetic remodeling of chromatin. The aim of the department is to characterize the influence of individual nuclear components and to define the role of subnuclear organelles in this process. Currently, the department‘s research focuses on the mechanism and role of active demethylation of the paternal genome after fertilization. Another topic is the impact of A‑ and B-type nuclear lamin depletion on early development.
Identification and characterisation of novel binding properties of the chromatin remodeling protein SMARCA5
We found that SMARCA5 specifically binds to divalent transient metals (Co, Cu, Zn, Ni) on solid supports. Isolation of protein and analysis of bonds were performed by immobilised metal affinity chromatography and quantum mechanics calculations, which resulted in spatio-energy models. The main importance of this work resides in possibilities to study functional interactions between transition metals and the SMARCA5 protein in the cell. These are: potential modulation of its nucleosome translocation activity and conformational changes within chromatin remodelling complexes.
Optimised structure of the zinc cation with the part of protein SMARCA5. The zinc atom (grey ball) complexed with the carboxymethyl aspartate resin forms bonds with the two histidine side chains on SMARCA5 protein fragment (violet ribbon). Model is based on B3LYP calculations; B3LYP approach belongs to density functional theory methods.
Publication:
Andrikopoulos, P. C, Čabart, P.: (2024) The chromatin remodeler SMARCA5 binds to d-block metal supports: Characterization of affinities by IMAC chromatography and QM analysis. PLoS One, Oct 7;19(10):e0309134. doi: 10.1371/journal.pone.0309134. eCollection, PMID: 39374200
The timing of pronuclear transfer critically affects the developmental competence and quality of embryos
Pronuclear transfer is a therapeutic approach used in several European countries. Irrespective of its successful use in human assisted reproduction, the exact protocol is often not described. We used a model of idiopathic developmental arrest to define the requirements for successfully applying this approach. We showed that the timing when pronuclear transfer is applied plays a major role, with the first embryonic replication being decisive for the subsequent embryo development. We therefore recommend using the pronuclear transfer in the early phases of the first embryonic cell cycle.
Replication stress during the first embryonic cell cycle is accompanied by replication stress. Replication stress can markedly impact embryo development, leading to its arrest. To better understand the replication stress effects, we developed a model systém, which allowed us to follow the long-term consequences on embryo development (top, markers of replication stress and DNA damage: RPA32, γH2A.X and Rad51). The model embryos can not suppress the replication stress, which leads to the accumulation of double-stranded DNA damage in the following embryonic cycle. By contrast, "healthy" embryos show neither signs of replication stress nor DNA damage.
Publication:
The timing of pronuclear transfer critically affects the developmental competence and quality of embryos. Znachorova T, Dudko N, Ming H, Jiang Z, Fulka H. Mol Hum Reprod. 2024 Jun 26;30(7):gaae024. doi: 10.1093/molehr/gaae024. PMID: 38991843
Nuclear lamins play a key role in mammalian development
Nuclear lamins are key nuclear proteins and at least one member of this family of proteins is detectable in the nucleus of the majority of cells. However, althought this might indicate that nuclear lamins are encoded by esential genes at the cellular level, their role especially in development remains highly controversial.
Lamin AC in early embryos. The presence of lamin AC has been traditionally linked to an advanced differentiation of cells. However, it is paradoxically also clearly detectable in mouse zygotes, which are totipotent.
Interspecific ICSI for the Assessment of Sperm DNA Damage
Xenogenic ICSI (intracytoplasmic sperm injection) can be used to evaluate the sperm DNA damage, which can radically influence the developmental potential of generated embryos. Sperm DNA damage, which can be for example caused by an inappropriate cryopreservation, is very hard to evaluate due to the compaction of sperm DNA caused by the association of the DNA with highly basic proteins, the protamines. Xenogenic remodeling, however, represents a relatively easy sperm DNA evaluation procedure even when the oocytes are scarce.
Zygote with the maternal and paternal pronucleus.
Publication:
Rychtařová, J., Langerová, A., Fulka, H., Loi, P., Benc, M., Fulka, J. Jr.: (2021) Interspecific ICSI for the Assessment of Sperm DNA Damage: Technology Report. Animals. 11(5): 1250. doi: 10.3390/ani11051250. PMID: 33926086
Projects
1. 3. 2022 – 28. 2. 2025
Molecular and functional analysis of the nucleolus in 3D genome organization during early embryo development
The AV21 Strategy program responds to the challenges of declining fertility and the growing importance of assisted reproduction.
Infertility affects spproximately 17.5% of population and is recognized by the World Health Organization as a disease with a profound impact on quality of life. At the same time, birth rates are declining worldwide—between 2016 and 2021 by 9%, and since the 1950s fertility have dropped by about half, with major socioeconomic impact on society. In response to these trends, the importance of assisted reproduction (ART) is steadily increasing. Since 1978, more than 10 million children have been born with the help of ART, representing 7.9% of all children born in Europe and 5.1% in the United States in 2018. Today, ART is the most effective treatment for infertility, therefore it is essential to connect clinical practice with biological research to prepare new methods, which will be used for inferetility treatment.
Department of Cell Nucleus PlasticityCzernik M.Palazzese L.Winiarczyk D.Iuso D.Khochbin S.Fulka J.Fulka H.Fulka H.Villafranca R.Rielo J. A.Sanchez-Rodriguez A.Latorre N.Agudo-Rios C.Roldan E. R. S.Teves M. E.Loi P.
2025
iScience . 2025 Jul 12;28(8):113102. doi: 10.1016/j.isci.2025.113102. eCollection 2025 Aug 15.
Department of Cell Nucleus PlasticityGioia L.Palazzese L.Czernik M.Iuso D.Fulka H.Fulka J. Jr.Loi P.
2024
Reproduction . 2024 Feb 2;167(3):e230360. doi: 10.1530/REP-23-0360. Print 2024 Mar 1.
2026
Reproduction, Volume 171, Issue 2, February 2026, Published: 23 January 2026