Recent advances in biomedical knowledge and techniques have greatly blurred the boundaries between physiology, cell biology, molecular genetics and biochemistry. The research themes addressed in URPhyM have in common the study of the molecular basis of normal biological functions and certain diseases. Find out more

The URPhyM brings together the following laboratories:

Laboratory of Cancer Molecular Biology (LBMC)

The development of multidrug resistance to chemotherapy remains a major challenge in cancer treatment. Resistance exists against all effective anticancer drugs and can develop through numerous mechanisms that lead to a state of multidrug resistance in tumor cells, in which cells become resistant to several drugs in addition to the initial compound administered.

ATP-binding cassette (ABC) transporters are key players in these mechanisms. In addition to their role in drug efflux, there is growing evidence that these transporters are involved in tumor biology.

ABCB5 is a member of the ABC transporter superfamily that is mainly expressed in pigment-producing cells. Previous studies have suggested that it is a marker of melanoma-initiating cells and is linked to the development of low-level multidrug resistance in cancer. Despite these reports, ABCB5 is poorly characterized.

Our current projects aim to:

• Discover the regulatory pathway of ABCB5 expression
Understand the physiological role of ABCB5 in vivo, using ABCB5-deficient mice
• To investigate the role of ABCB5 as a marker of melanoma initiating cells using knock-in
• Studying the role of ABCB5 in melanoma biology

Laboratory for Intracellular Traffic Biology (LBTI)

Lysosomes are acidified intracellular organelles containing nearly 60 different acid hydrolases. This broad arsenal of proteins ensures the breakdown of macromolecules delivered to lysosomes by endocytosis or autophagy into primary components that can be recycled back into the cytosol to reintegrate biosynthetic reactions. This recycling function depends on the numerous transporters integrated into the lysosome limiting membrane. When they are unable to degrade macromolecules or translocate their degradation products to the cytosol, abnormal accumulation of material in lysosomes leads to lysosomal and cellular dysfunction. To date, some 50 lysosomal overload diseases have been reported, many of them characterized by neurodegeneration, severe organ failure and premature death. Lysosomal alterations have also been associated with the negative evolution of other pathologies, including cancer, atherosclerosis and Alzheimer's and Huntington's diseases. Interestingly, there is growing evidence that lysosomes not only degrade macromolecules, but also control cell growth and survival by serving as signaling platforms.

The study of the underlying causes of lysosomal dysfunction has shown that to maintain a well-oiled lysosomal machine and thus prevent deleterious cellular/tissue alterations, cells must express all the required lysosomal and lysosome-associated proteins, but more importantly, they must target them efficiently and specifically to the lysosomal compartment. To meet this second requirement, cells rely on several intracellular trafficking mechanisms that transport newly synthesized lysosomal soluble or membrane proteins to their site of residence within the cell.

In the laboratory, we are particularly interested in these transport mechanisms, as well as lysosomal functions in general. In particular, we use a variety of models to investigate the underlying causes and consequences of lysosomal storage disorders and other lysosome-associated diseases, with an emphasis on issues related to subcellular trafficking.

Laboratory Cells and Tissues (LabCeTi)

The research unit focuses on cutaneous biology and pathology approached through morphological and functional approaches: control of proliferation, differentiation, and adhesion of epidermal keratinocytes and cutaneous immunity.

Virtual microscope: www.histology.be

Digital microscopic morphology atlas:

• General history
• Special human history
• Special animal history

Laboratory of Physiological Chemistry (MBICP)

The general research theme is the study of subcellular organelles and membrane trafficking under normal and pathological conditions. It is centered on lysosomes.

Genetics laboratory (MBIG)

Function of MAGE proteins in mice.

The mMage-a and mMage-b genes are specifically expressed in male germline cells and in some cancer cells. MAGE-D genes differ in their ubiquitous expression profile, higher degree of conservation and genomic organization. To elucidate the function of MAGE proteins, we set out to produce deficient mouse lines. The two-hybrid technique is used to identify protein partners.

Molecular Genetics Laboratory (GéMo)

How a single genome can encode the blueprint of a complex organism with highly differentiated cell and tissue types is one of biology's oldest questions.

The generation of specific cell types depends on spatial and temporal regulations of gene expression. Of the three RNA polymerases, RNA polymerase II (Pol II) is the enzyme responsible for the synthesis of messenger RNA and most small RNAs in eukaryotic cells.

Studies over the decades have revealed many aspects of the composition, structure and enzymatic activity of its subunits. They have also revealed that many steps in gene expression, initially thought to be independent, are intricately coordinated in a regulated network, and that the central coordinator that couples this regulatory network is a simple tandem iterated sequence: the C-terminal domain (CTD) of the largest Pol II subunit, Rpb1.

The CTD comprises heptadic repeats of a conserved YSPTSPS consensus sequence that serves as a dynamic surface for the recruitment of proteins required for mRNA co-transcriptional processing or histone modifications.

The timely recruitment of mRNA processing factors is ordered according to modifications within the heptad. Five of the seven residues can be phosphorylated or glycosylated, and proline residues can exist in both cis or trans stereoisomeric states.

The combinatorial complexity of the resulting modification scheme is referred to as the CTD code, although its biological significance remains to be explored.

Best characterized are changes in the CTD serine phosphorylation pattern during transcription, which are both temporally and functionally coupled to the association of RNA processing complexes.

As a result, RNA polymerase II, rather than being the execution engine of gene transcription, functions as a central processor integrating and processing a multitude of environmental cues. In our laboratory, we use fission yeast to understand how changes in the CTD of RNA polymerase II are regulated during cell differentiation.

Laboratory Neurodegeneration and Regeneration (LNR)

Understanding the pathophysiology of neurodegenerative diseases in animal models and developing stem cell therapies for neurodegenerative diseases.

Professor Charles Nicaise heads the Neurodegeneration and Regeneration Laboratory (NRL), dedicated to understanding the pathophysiology of neurological disorders in animal models and developing stem cell therapies.

His laboratory is interested in examining the in vivo role played by glial cells and their function in glutamate homeostasis during osmotic demyelination syndrome (ODS) and spinal cord injury (SCI). We have recently focused on the Xc- system, a cystine/glutamate antiporter involved in both antioxidant defense and the regulation of glutamate neurotransmission. Using a multidisciplinary approach that includes animal models, transgenic and knock-out mouse models, stem cell transplantation (glial precursor cells or iPS-derived neuronal precursors), viral vector-mediated intraspinal manipulation of glutamate transporter levels and extensive in vivo histological, biochemical, behavioral and physiological analyses, their aim is to characterize the roles played by these glial glutamate transporters in clinically relevant models of ODS or SCI.

The laboratory has developed considerable expertise in creating rodent models of contusive cervical spinal cord injury. In this context, another topic of interest is the characterization of innovative non-invasive imaging modalities aimed at quantifying neuronal or synaptic loss following spinal cord injury, e.g. synchrotron X-ray phase contrast tomography, SV2A PET imaging using [11C]UCB-J. Discover the list of publications: https://researchportal.unamur.be/fr/persons/nicaisec

Members:

Scientific collaborator: Prof. Emeritus Jacques Gilloteaux

Current PhD students: Lindsay Sprimont and Nicolas Halloin

Alumni: Dr. Joanna Bouchat & Sarah Michel

Contact: charles.nicaise@unamur.be

Laboratory of General Physiology (MMEPG)

Research in the laboratory emphasizes an integrated approach to understanding the pathophysiological mechanisms of renal failure using animal models. The specific skills developed here relate in particular to the study of intrarenal hemodynamic regulation as well as excretory function in vivo.

Laboratory of Physiology and Pharmacology (MMEPP)

1. Role of the inner medullary zone of the kidney in hydroelectrolytic balance and essential hypertension.
2. Study of hyaluronan and hyaluronidases.
3. Role of endothelin in cancer proliferation.

Laboratory of Respiratory Physiology (LPR)