Recent advances in biomedical knowledge and techniques have greatly blurred the boundaries between physiology, cell biology, molecular genetics, and biochemistry. The research topics addressed at URPhyM share a common focus on studying the molecular basis of normal biological functions and certain diseases. Find out more on the UNamur research portal.

The URPhyM comprises the following laboratories: 

Laboratory of Molecular Biology of Cancer (LBMC) 

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

ABC (ATP-binding cassette) 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 primarily expressed in pigment-producing cells. Previous studies have suggested that it is a marker of melanoma-initiating cells and that it is linked to the development of low-level multidrug resistance in cancer. Despite these reports, ABCB5 is poorly characterized. 

Our ongoing projects aim to:

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

Intracellular Traffic Biology Laboratory (LBTI) 

Lysosomes are acidified intracellular organelles that contain nearly 60 different acid hydrolases. This large arsenal of proteins ensures the breakdown of macromolecules delivered to lysosomes by endocytosis or autophagy into primary components that can be recycled in the cytosol to re-enter biosynthesis reactions. This recycling function depends on the many transporters that are integrated into the lysosome membrane. When they are unable to break down macromolecules or translocate their degradation products to the cytosol, the abnormal accumulation of material in the lysosomes causes lysosomal and cellular dysfunction. To date, approximately 50 lysosomal storage disorders have been reported, many of which are characterized by neurodegeneration, severe organ failure, and premature death. Lysosomal alterations have also been linked to the negative progression of other diseases, 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. 

Studies of the underlying causes of lysosomal dysfunction have shown that in order to maintain a well-oiled lysosomal machine and thus prevent deleterious cellular/tissue alterations, cells must express all the required lysosomal proteins 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 soluble or membrane lysosomal proteins to their site of residence within the cells. 

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

NanoChimera Lab (NaCL) 

The NanoChimera Lab focuses on the design and production of chimeric proteins with the aim of generating new methods for research in cell biology or developing new experimental and original therapies. Our laboratory has particular expertise in the production and use of recombinant proteins, specifically nanobodies (nano-antibodies derived from heavy chain immunoglobulins found only in camelids). We produce our proteins using prokaryotic (E. coli) and eukaryotic (EXPI 293™) expression systems.

The laboratory also has expertise in the use of sortase A to conjugate the proteins we produce to all kinds of molecules and/or proteins by transpeptidation. 

Our research is currently focused on designing new and original therapies to treat cancer, using lectins, sugar-binding proteins, to specifically recognize cancer cells. Our team uses in vitro and in vivo models of melanoma, colon cancer, and pancreatic cancer for this purpose. 

We are also studying the conjugation of cytokines, (subdomains of) proteins belonging to the DAMPs class, and various enzymes to nanobodies to stimulate the immune rejection of tumor cells.

The NanoChimera Lab occupies the space previously dedicated to the Cell and Tissue Laboratory (LabCeTi), founded by Professor Emeritus Yves Poumay, which focused on skin biology and pathology using morphological and functional approaches. We retain technical expertise in these areas thanks to the know-how of the LabCeTi team members who have joined NaCL.

Virtual microscope: www.histology.be 

Digital atlas of microscopic morphology:  

• General histology
• Special human histology
• Special animal histology 

Contact: Thomas Balligand 

More information about the NaCL laboratory on the NARILIS Institute website

Read our newsroom article on Thomas Balligand

Physiological Chemistry Laboratory (MBICP) 

The general research theme is the study of subcellular organelles and membrane trafficking under normal and pathological conditions. It focuses 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 certain cancer cells. MAGE-D genes differ in their ubiquitous expression profile, their higher degree of conservation, and their genomic organization. To elucidate the function of MAGE proteins, we have undertaken the production of deficient mouse lines. The double hybrid technique is used to identify protein partners. 

Molecular Genetics Laboratory (GéMo) 

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

The generation of specific cell types depends on the spatial and temporal regulation 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 conducted over 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 coordinated in a complex manner within a regulated network, and that the central coordinator that couples this regulatory network is a simple tandemly repeated sequence: the C-terminal domain (CTD) of the largest subunit of Pol II, Rpb1. 

The CTD comprises heptad repeats of a conserved YSPTSPS consensus sequence that serves as a dynamic surface for the recruitment of proteins necessary for co-transcriptional mRNA 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 the proline residues can exist in either the cis or trans stereoisomeric states. 

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

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

Therefore, RNA polymerase II, rather than being the engine driving 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 RNA polymerase II CTD modifications are regulated during cell differentiation. 

Neurodegeneration and Regeneration Laboratory (LNR) 

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

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

His laboratory is interested in examining the in vivo role of 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 knockout mouse models, stem cell transplantation (glial precursor cells or iPS-derived neural precursors), intraspinal viral vector manipulation of glutamate transporter levels, and in-depth in vivo histological, biochemical, behavioral, and physiological analyses, their goal is to characterize the roles played by these glial glutamate transporters in clinically relevant models of ODS or SCI. 

The laboratory has developed extensive 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, such as synchrotron X-ray phase contrast tomography and SV2A PET imaging using [11C]UCB-J. See the list of publications: https://researchportal.unamur.be/fr/persons/nicaisec

Members: 

Scientific collaborator: Professor Emeritus Jacques Gilloteaux 

Current doctoral students: Lindsay Sprimont and Nicolas Halloin 

Alumni: Dr. Joanna Bouchat & Sarah Michel 

Contact: charles.nicaise@unamur.be

General Physiology Laboratory (MMEPG) 

The research conducted in the laboratory focuses on an integrated approach to understanding the pathophysiological mechanisms of renal failure using animal models. The specific skills developed there relate in particular to the study of intrarenal hemodynamic regulation and excretory function in vivo.   

Physiology and Pharmacology Laboratory (MMEPP) 

1. Role of the inner medulla of the kidney in water and electrolyte balance and in essential hypertension.
2. Study of hyaluronan and hyaluronidases.
3. Role of endothelin in cancer proliferation. 

Respiratory Physiology Laboratory (LPR)