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Rapid methods of prevention, diagnostics and therapeutic treatment of polycystic kidney disease (PKD):
Spain (IFMSA-SPAIN)-University of Santiago de Compostela, Santiago de Compostela
Nephrology Lab, Biology and genetics of kidney diseases of Health Research institute
Dr. Miguel Garcia Gonzalez
Dr. Miguel Garcia Gonzalez
Required: English, Accepted: Spanish
Type of Research Project
- Clinical Project with Laboratory work
What is the background of the project?
Polycystic disease (PD) involves a pathological phenomenon known as cystogenesis, characterized by the progressive loss of tubular shape becoming enlarged cysts and altering the structure and function of the kidney (PKD), liver (PLD) and pancreas (PPD). PKD by itself affects an estimated 12.5 million people worldwide, what makes PD one of the most common inherited disorders and a public health problem of the first magnitude in the world. PD has been proposed also as a ciliopathy, where cilia driven mechanisms like mechano- and chemo-sensation, cell shape and polarization, as well as transduction of a variety of signaling cascades seems to be altered. However, under the current state-of-the-art, many of these mechanisms driving cystogenesis are controversial, diagnosis and disease onset are difficult to anticipate without family history, and the harsh reality is that no target therapies other than dialysis or organ replacement have been established for this disorder. Supporting evidences suggest that the control of the disease in early stages or prior to cyst formation could be a determining factor in its prevention. We intend to develop a multidisciplinary approach that helps us to determine the “cell of origin” of cysts, to identify developmental signalling pathways participating in cystogenesis, and finally to develop the necessary tools to treat, diagnose and predict the onset of PD.
What is the aim of the project?
To achieve these tasks, this project is organized in work packages of increasing degrees of novelty and complexity. WP1: To temporally and spatially characterize cyst formation in a developing organ, with a specific focus on progenitor cell behavior. WP2: To further confirm the cell-of-origin in which cyst formation originates. WP3: To develop a model that will allow us to easily track and study the molecular mechanisms evolving cystogenesis and test potential disease therapies. WP4: To develop a diagnostic tool to anticipate the type and onset of all human PDs in a reliable, efficient and quick manner in patients lacking family history and who have not yet develop the disease. In summary, the PDCURE project will develop innovative strategies to provide knowledge of the disease mechanisms, early diagnosis and treatment of polycystic diseases.
What techniques and methods are used?
basic laboratory techniques (cell culture, molecular biology, western blot, RNA/DNA processing, RealTime PCR, ...), high-throughput screening.
What is the role of the student?
- If the project includes “lab work”
- the student will take active part in the practical aspect of the project
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
Basic understanding and knowledge about Hereditary Renal Diseases and genetics. The practical learning will depend on the student and his/ her previous knowledges and his/her actitud to adquire new ones.
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?
- The student will prepare a scientific report
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Minimal knowledge of lab routine (for example: solution preparation, calculate concentrations
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Pre-Medical students from the American-British system
- Rezende-Lima W; Parreira KS; García-González M; Riveira E; Banet JF; Lens XM. Homozygosity for Uromodulin disorders: FJHN and MCKD type 2. Kidney Inter.; 2004; 66:1-6.
- Garcia-Gonzalez MA; Menezes LF; Piontek KB; Kaimori J; Huso DL; Watnick T; Onuchic LF; Guay-Woodford LM; Germino GG. Genetic interaction studies link the major loci responsible for human ADPKD and ARPKD in a common pathway. Hum. Mol. Genet. 2007 Aug 15;16(16):1940-50.
- Garcia-Gonzalez MA; Jones JG; Allen SK; Palatucci CM; Batish SD; Seltzer WK; Lan Z; Allen E; Qian F; Lens XM; Pei Y; Germino GG; Watnick TJ. Evaluating the Clinical Utility of a Molecular Genetic Test for Polycystic Kidney Disease. Mol. Genet. Metab. 2007 Sep;92 (1-2): 160-167.
- Piontek K; Menezes LF; Garcia-Gonzalez MA; Huso DL; Germino GG. A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1. Nat Med. 2007 Dec;13(12):1490-5.
- Miguel A. Garcia-Gonzalez; Patricia Outeda; Qin Zhou; Fang Zhou; Luis F. Menezes; Feng Qian; David L. Huso; Gregory G. Germino; Klaus B. Piontek; Terry Watnick. Pkd1 and Pkd2 are Required for Normal Placental Development. PLoS One. 2010 Sept 16;5(9). pii: e12821.
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