Projects
Name
Functional analysis of newly identified epidermal proteins: involvement in the terminal differentiation of keratinocytes and epidermal barrier functio
University
France (ANEMF) - University of Toulouse, Toulouse
Domain
Pathology
Departement
UMR 5165 CNRS - Hopital Purpan, Place du Docteur Baylac TSA 40031 - 31059 TOULOUSE
Head
Professeur Guy SERRE
Tutor
Nathalie JONCA (PhD)
Languages
French, English
Duration
4 weeks
Availability
Cities/Months Jan Feb Mar Apr May Jun Jul Augt Sep Oct Nov Dec
No No No No No Yes Yes No No No No No
Type of Research Project
- Basic science
What is the background of the project?
Terminal differentiation of the epidermis is an oriented process during whichkeratinocytes of the innermost basal layer undergo a series of metabolic and structural changes as they migrate toward the skin surface. At the latest stage, they undergo cornification, a programmed cell death leading to the transformation of granular keratinocytes, the last living cells in the program of keratinocyte terminal differentiation, into corneocyte. The cornified layer, resulting from the stacking of corneocytes, is essential for the main function of epidermis, the barrier function, vital for the organism.
Thus at the granular keratinocyte stage culminates the production of the cornified envelope precursors as well as other cellular components specific for the stratum
corneum.
The essential role of the epidermal barrier is largely demonstrated by the consequences of its alteration during various dermatological diseases, especially numerous genodermatoses such as Lamellar Ichthyosis, X-linked Ichthyosis or the Netherton Syndrome, which are related to mutations of genes expressed only at late stages of keratinocyte differentiation.

Our group works on the structural, cellular and molecular basis of the barrier function of the stratum corneum. More particularly, we are interested in two essential functional properties of the epidermal barrier: the stratum corneum cohesion and its mechanical resistance, studies through investigation on the cornified envelope and an adhesive protein of the corneodesmosome, corneodesmosin (CDSN).
A second objective of the group is to decipher the pathophysiology of some yet poorlycharacterized ichthyoses, including the Peeling Skin Disease, a rare disease that was recently shown to result from nonsense mutation in CDSN.

What techniques and methods will be used? Functional studies imply in vitro experiments (identification of putative molecular partner, characterization of enzymatic function...) as well as in vivo experiments (transfection of eukaryotic cells, mouse models). We have a broad technical equipment to achieve experiments from various fields like biochemistry (SDS-PAGE, protein purification), molecular biology (cloning, PCR, RT-PCR) and immunohisto(cyto)chemistry (microscopy, confocal microscopy,
western blotting, immunoprecipitation...).
The student will acquire basis on current techniques of molecular and cellular biology, as well as protein biochemistry. He will acquire knowledge on cellular biology, more particularly in the field of dermatology (keratinocyte differentiation, epidermal barrier function).

Bibliography:
Jonca N, Guerrin M, Hadjiolova K, Caubet C, Gallinaro H, Simon M, Serre G.
Corneodesmosin, a component of epidermal corneocyte desmosomes, displays homophilic adhesive properties.
J Biol Chem 277:7, 5024-5029, 2002

Levy-Nissenbaum E, Betz RC, Frydman M, Simon M, Lahat H, Bakhan T, Goldman B, Bygum A, Pierick M, Hillmer AM, Jonca N, Toribio J, Kruse R, Dewald G, Cichon S, Kubisch C, Guerrin M, Serre G, Nothen MM, Pras E.
Hypotrichosis simplex of the scalp is associated with nonsense mutations in CDSN encoding corneodesmosin.
Nat Genet 34:2, 151-153, 2003

Toulza E, Galliano M-F, Jonca N, Gallinaro H, Mechin MC, Ishida-Yamamoto A, Serre G, Guerrin M.
The human dermokine gene: description of novel isoforms with different tissue-specific expression and subcellular location.
J Invest Dermatol 126:2, 503-506, 2006

Galliano M-F, Toulza E, Gallinaro H, Jonca N, Ishida-Yamamoto A, Serre G, Guerrin M.
A novel protease inhibitor of the alpha2-macroglobulin family expressed in the human epidermis.
J Biol Chem 281:9, 5780-5789, 2006

Toulza E, Mattiuzzo NR, Galliano M-F, Jonca N, Dossat C, Jacob D, de Daruvar A, Wincker P, Serre G, Guerrin M.
Large-scale identification of human genes implicated in epidermal barrier function.
Genome Biol 8:6, R107, 2007
What is the aim of the project?
What techniques and methods are used?
What is the role of the student?
- The student will mainly observe
What are the tasks expected to be accomplished by the student?
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Basic skills are required in cellular biology and biotechnology. Knowledge on cutaneous biology is not abselutely required. There are no legal limitations in the student
Are there any legal limitations in the student’s involvement
No
Hours
6
Type of students accepted
This project accepts:
- Medical students
Articles
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