PhD - Structural characterization of cystathionine beta-synthase enzyme

CIC bioGUNE

Bilbao, Spain

 

Description

 

The laboratory of Dr. Alfonso Martínez at CIC bioGUNE is searching a ph.D. candidate to apply for the next Basque Government Call (Programa Predoctoral de Formación de Personal Investigador). The successful candidate will work in the structural characterization of cystathionine beta-synthase enzyme (CBS). Cystathionine beta-synthase is a pyridoxal-5’-phosphate (PLP)-dependent enzyme, which plays a pivotal role in sulfur amino acid metabolism. CBS catalyzes a beta-replacement reaction, where the hydroxyl group of L-serine (Ser) is replaced by L-homocysteine (Hcy) yielding cystathionine (Cth). Hcy is a non-essential amino acid synthesized from L-methionine (Met) via transmethylation and is a well-recognized multisystem toxic substance. Increased plasma level of Hcy, chiefly due to CBS deficiency, represents an independent modifiable risk factor for thrombosis, atherosclerosis and vascular disease. CBS-deficient homocystinuria (CBSDH) is an autosomal, recessive inborn error of metabolism resulting from pathogenic mutations in both CBS alleles. In addition to increased Hcy levels, CBSDH is biochemically characterized by very high Met, S-adenosyl-L-methionine (AdoMet), and S-adenosyl-L-homocysteine (AdoHcy) levels, decreased Cys and very low Cth levels. Clinical symptoms manifest themselves in the ocular, skeletal, vascular and central nervous systems. Untreated patients suffer from connective tissue defects such as dislocated optic lenses and multiple skeletal deformities. Vascular thromboses may lead to a fatal stroke early in life and there is often mental retardation diagnosed in the affected patients. In addition to its crucial role in the sulfur amino acid metabolism, CBS has recently been implicated as major physiological source of hydrogen sulfide (H2S), the third physiological gasotransmitter joining nitric oxide and carbon monoxide. H2S is an important signaling molecule in the cardiovascular and nervous systems, induces smooth muscle relaxation and has antiinflammatory and cytoprotective effects on cells

 

Requirements

 

Candidates must comply with the call requirements regarding university scores (mandatory >1.6 but encouraged >2) and place of residence (CAPV).

 

More information and applications

 

Interested applicants should e-mail to rrhh@cicbiogune.es with ref. 3141 in the subject including the following information:

 

1. A cover letter
2. Your CV including the BA/BSc qualification on a scale 1-4
3. Names (including e-mail address) of at least two referees

Dead line for applications to be considered: 15-Jul-2013