Research
Current molecular and genetic research conducted at the Biology Department falls under four major research themes:
1. Laboratory of Pathophysiological Cell Signaling
2. Developmental and Cell Stem Biology
3. Insect Physiology
4. Molecular Bacteriology
1. Cell Cycle Control
(led by Prof. Dr. Gustavo J. Gutierrez)
The Cell cycle Control (CCC) group is interested in understanding at the genetical, cellular, and biochemical levels how cells proliferate. In mammals, the cell cycle is frequently divided in four phases known as G1, S (or DNA replication), G2, and M (or mitosis). We study proteins and proteins complexes that control the transition through the different phases of the cell cycle. Our efforts are focused on signal transduction pathways, involved in cell division, which are regulated by protein phosphorylation and/or ubiquitination. Hence, we have a broad interest in protein kinases/phosphatases and ubiquitin ligases/deubiquitinating enzymes acting along the cell cycle and associated checkpoint responses.
Specific research topics of the CCC group are:
- Control of the cell cycle by the protein kinase c-Jun N-terminal Kinase (JNK) and other related stress-activated pathways;
- Function and Regulation of the Anaphase-Promoting Complex or Cyclosome (APC/C) ubiquitin ligase;
- Neural differentiation of human embryonic and induced-pluripotent stem cells.
We employ both classical and cutting-edge biochemical and cellular biology-related methodologies mostly using at the moment tissue culture systems that include normal, cancer, and stem cells. We expect to apply our knowledge and expertise to mouse animal models in the near future.
Selected publications:
Gutierrez GJ, Tsuji T, Cross JV, Davis RJ, Templeton DJ, Jiang W, Ronai Z (2010) JNK-mediated phosphorylation of Cdc25C regulates cell cycle entry and G2/M DNA damage checkpoint. J Biol Chem 285: 14217–14228.
Gutierrez GJ, Ronai Z (2006) Ubiquitin and SUMO systems in the regulation of mitotic checkpoints. Trends Biochem Sci 31: 324–332.
Gutierrez GJ, Vogtlin A, Castro A, Ferby I, Salvagiotto G, Ronai Z, Lorca T, Nebreda AR (2006) Meiotic regulation of the CDK activator RINGO/Speedy by ubiquitin-proteasome-mediated processing and degradation. Nat Cell Biol 8: 1084–1094.
2. Developmental and Cell Stem Biology
(led by Prof. Dr. Luc Leyns)
In the Developmental and Stem Cell Biology group, we focus on:
- The role of the several signaling pathways involved in patterning and differentiation in the mouse embryo;
- Modeling the embryonic development by differentiating in vitro embryonic stem cell into muscle, cardiac or neural cells and
- Analyzing the toxic effect of nanoparticles on mouse embryonic stem cells (mES).
Our challenge is to understand how cells know their position in the embryo and react upon it by proliferating, migrating and differentiating to form the embryo. To address these questions we are studying the role of secreted molecules during the early phase of development when an embryo composed initially of a few thousand pluripotent cells will be organized in three germ layers (ecto-, meso- and endoderm) with an antero-posterior axis and a dorso-ventral axis. To strengthen the results obtained by studying embryos, we are analyzing the signals triggering the differentiation of mES cells. More applied research is also performed on the effects of nanoparticles on mES cells, used as models for embryonic development. More specifically the (embryotoxic) effects of nanoparticles on the differentiation of mES cells is investigated at morphological as well as molecular level. Furthermore the underlying pathways responsible for these changes are being studied.
Selected publications:
Kogan Y, Halevi-Tobias KE, Hochman G, Baczmanska AK, Leyns L, Agur Z (2012). A new validated mathematical model of the Wnt signalling pathway predicts effective combinational therapy by sFRP and Dkk. Biochem J 444: 115–125.
Hendrickx M, Van XH, Leyns L (2009). Anterior-posterior patterning of neural differentiated embryonic stem cells by canonical Wnts, Fgfs, Bmp4 and their respective antagonists. Dev. Growth Differ 51: 687–698.
Willems E, Leyns L (2008). Patterning of mouse embryonic stem cell-derived pan-mesoderm by Activin A/Nodal and Bmp4 signaling requires Fibroblast Growth Factor activity. Differentiation 76: 745–759.
3. Insect Physiology
(led by Prof. Dr. Ir. Guy Smagghe)
In the “Insect Physiology group” we perform applied and fundamental research with the social insect Bombus terrestris (bumblebee).
B. terrestris is of major ecological and economical importance due to its world wide use for the pollination of various crops.
In the lab we have three major lines of research:
- Risk assessment of the use of pesticides/pollutants with B. terrestris. Here the group has a major position and could already developed several laboratory bioassays to evaluate potential lethal and sublethal effects on reproduction and on behavior following acute/chronic exposure to pesticides/pollutants.
- Entomovector technology as an environmentally friendly strategy to control important plant pathogens/pests. This technology makes use of pollinators to transport (bio)pesticides directly to the flowers of crops while foraging. Research on this subject concentrates on the development of bioassays to assess potential side-effects and on the efficiency of transport (e.g. formulations, carriers and dispensers).
- Insect communication. The communication between insects and between insects and plants relies on the perception of environmental stimuli. In the laboratory we study the behavior of foraging and on chemical communication by identifying the key elements which regulate this behavior (role and function of genes).
Selected publications:
Mommaerts V, Reynders S, Boulet J, Besard L, Sterk G, Smagghe G (2010). Risk assessment for side-effects of neonicotinoids against bumblebees with and without impairing foraging behaviour. Ecotoxicology 19: 207–215.
Mommaerts V, Smagghe G (2011). Entomovectoring in plant protection. Arthropod-Plant Interactions 5: 81–95.
Tobback J*, Mommaerts V*, Vandersmissen HP, Smagghe G, Huybrechts R (2011). Age and task dependent foraging gene expression in the bumblebee Bombus terrestris. Archives of Insect Biochemistry and Physiology 76: 30–42. (* equally contributed).
4. Molecular Bacteriology
(led by Prof. Dr. Jean-Pierre Hernalsteens)
This research group investigates the molecular basis of the interaction of pathogenic bacteria (e.g. Escherichia coli, Salmonella enterica and Staphylococcus aureus) of humans and domestic animals with their host. This is performed by the identification of genes playing a key role in the various stages of the infection process. The genetic research is facilitated by the newly developed high-performance methods for the analysis of bacterial genome sequences. Worldwide an alarming increase of the antibiotic resistance of pathogenic bacteria is reported. Therefore alternative methods for the prevention and treatment of bacterial infections of humans and farm animals are tested. The research group produced efficient live Salmonella vaccine strains with well-defined deletion mutations for the protection of chickens against Salmonella infections. Also bacteriophages, viruses that infect bacteria, are isolated, characterized and tested for this purpose. Some proteins, which these bacteriophages use to infect and kill their host, are also strongly bactericidal and are purified and tested as alternatives to traditional antibiotics. For the infection tests, tissue cultures and surrogate hosts, such as the nematode Caenorhabditis elegans and the greater wax moth Galleria mellonella are preferentially used.
Selected publications:
Derous V, Deboeck F, Hernalsteens J-P, De Greve H (2011). Reproducible gene targeting in recalcitrant Escherichia coli isolates. BMC Res Notes 4: 213.
Van Gerven N, Derous V, Hernalsteens J-P (2008). Expression of in vivo-inducible Salmonella enterica promoters during infection of Caenorhabditis elegans. FEMS Microbiol Lett. 278: 236–241.
Adriaensen C, De Greve H, Tian JQ, De Craeye S, Gubbels E, Eeckhaut V, Van Immerseel F, Ducatelle R, Kumar M, Hernalsteens J-P (2007). A live Salmonella enterica serovar Enteritidis vaccine allows serological differentiation between vaccinated and infected animals. Infect Immun 75: 2461–2468.