סמינר המחלקה להנדסה ביו רפואית

ליאור טריימן

תלמידת המחלקה להנדסה ביו רפואית לתואר שני תרצה בנושא:

A computational study about the effect of oscillations in translation factors on translation rate

Gene  expression  is  a  central  cellular  process  by  which  the  protein  coding  potential inscribed in the DNA is converted into proteins. Translation, is an important step of gene expression. It is the process by which messenger RNA (mRNA) is decoded by a ribosome to produce a specific amino acid chain – protein. This fundamental process is related to all biomedical disciplines. Specifically, it may be engineered for various biotechnological applications. Oscillations and clocks are important components of many hardware systems, suggesting that they are required also in synthetic biology. As timing is a key factor in most engineered systems and also driving biological processes, this work focuses on the effect of oscillations on gene translation.

Effect of oscillations in tRNA pool levels, as well as oscillations in codon translation rates in different locations in the gene strand, were studied using the Totally Asymmetric Simple Exclusion Process (TASEP) as implemented in Matlab. This computational model takes into consideration the interactions between ribosomes and their size, concentration of tRNA molecules, efficiency of their interaction with codons, and the stochastic nature of translation.

 This is the first work done exploring oscillation in translation factors using simulations in a computational model that takes into consideration the bio-physical nature of translation process, it is a genome scale analysis using real data parameters including ribosome size, typical decoding times and real genes from the yeast genome.

Results suggest oscillating translation factors results in a periodic translation rate. A strong negative Spearman correlation (P<10^-87) exists between gene length and gene's translation rate amplitude. Moreover, the change of -10% in gene length has a stronger effect on translation rate amplitude (+34%) than in long genes (+9%). Furthermore, there is a strong positive Spearman correlation (P<10^-87) between the oscillated codon efficiency and genomic mean amplitude of translation rate, such that a change in +20% of oscillated codon velocity results in +40% increase and translation rate amplitude. In total about 200% change in translation rate amplitude is controlled by the oscillated codon velocity. Another connection was found between the relative locations of oscillation in the gene. When oscillating codons in the middle of the genes ORF it has a ~15% higher genomic mean amplitude comparing with oscillating codons on the edge (upstream) of the gene.

העבודה נעשתה בהנחיית  דר' תמיר טולר, המחלקה להנדסה ביו-רפואית,

אוניברסיטת תל-אביב

ההרצאה תתקיים ביום ראשון 15.03.15, בשעה 14:15,

בחדר 315, הבניין הרב תחומי, אוניברסיטת תל אביב