1. Epigenetic control of gene silencing
Transgene silencing in plants is a well-documented phenomenon. In general, the insertion of a particular gene into a plant may cause the silencing of homologous native or transgenic genes. In many cases, a transgene engenders silencing of a native gene (co-suppression) as well as of itself, but few cases of silencing of a single, unique insertion, such as that of a reporter gene have been recorded. It has been established that epigenetic mechanisms control gene expression through gene silencing occurring at the transcriptional (TGS), or posttranscriptional (PTGS) levels. Both types of silencing are associated with cytosine methylation, the most common epigenetic modification of DNA higher eukaryots.
The work focuses on:
- Studies of developmental and environmental control of gene silencing
- Dynamics and evolution of silent state
- Chemical drugs that interfere with gene silencing
- Inheritance and maintenance of silence state
- Molecules mediating genetic and epigenetic interactions between homologous loci
2. Genetics of allopolyploid nucleus
Polyploidy, in which the entire chromosome complement multiplies (3x, 4x?), is widespread in angiosperms, indeed up to 80% of species may be polyploids and sequence data suggest that even apparently ?diploid? species are, in fact, palaeopolyploids. When polyploidy occurs after interspecific hybridisation the process is called allopolyploidy. Allopolyploidy restores fertility to newly formed hybrids, a driving force behind sympatric speciation in plants. A consequence of allopolyploidy is the bringing together of diverged sequences from different species into the same genome.
The primary research objective is to understand the implication of plant polyploidy on plant evolution, plant genome structure, genome dynamics and organisation, systematics and biodiversity.
The work focuses on:
- Genetic interactions in allopolyploid nucleus
- Epigenetic inactivation of ribosomal gene expression - nucleolar dominance phenomenon
- Evolution of genomes in ancient (Nicotiana) and recent (Tragopogon) allopolyploids
- Construction of synthetic allopolyploids
3. Evolution of satellite repeats
The term satellite DNA was originally assigned to those parts of a genome that can be separated from the majority of DNA by buoyant density gradient centrifugation, i.e. the density of satellite DNA or, in other words, the AT/GC-content should differ from the mainband DNA. A single highly repetitive satellite may occupy large parts of the eukaryotic genome (up to 50% in some insects). Some repeats occur in a large number of members of a given genus whereas others are specifically present in one or a few species. They also appear to be amplified in different degrees within wild species and cultivated species of higher plants. Satellite DNA is expected to evolve according to the concept of ?concerted evolution?; typically the numerous copies of a satellite DNA family show high levels of intraspecific sequence similarity contrasting a relatively high interspecific diversity with respect to sequence and/or copy number.
The work focuses on:
- Isolation and characterisation of satellite repeats from different plant species
- Spreading of satellite repeats along the chromosomes
- Satellite expansion/contraction in allopolyploid genomes
- Structural properties of satellite DNA
- Epigenetic modification of satellite repeat chromatin
4. Development of epigenetic drugs
Epigenetic mechanisms based on covalent modifications of chromatin play important role in a number of fundamental biological processes, e.g. transcription, recombination, DNA elimination. At the cellular and organism level, epigenetic tools regulate switches between heterochromatin and euchromatin, imprinting and various developmental processes. Changes in epigenetic programming are involved in many human diseases including cancer suggesting that there is an ultimate need to develop drugs acting on epigenetic pathways. Most eukaryotic organisms evolved methylation of lysine amino acid residues of histone proteins and methylation of cytosine in DNA. The methylation is catalysed by specific enzymes that might be inhibited at different levels. We now aim to develop new inhibitors of DNA and histone methylation.
The work focuses:
- inhibitors of S-adenosylmethionine and S-adenosylhomocysteine biosynthetic pathways altering methylation cofactor pools
- inhibitors of DNA methylation based on nucleoside analogs