Toward Engineering Biosystems With Emergent Collective Functions

Many complex behaviors in biological systems emerge from large populations of interacting molecules or cells, generating functions that go beyond the capabilities of the individual parts. Such collective phenomena are of great interest to bioengineers due to their robustness and scalability. However, engineering emergent collective functions is difficult because they arise as a consequence of complex multi-level feedback, which often spans many length-scales. Here, we present a perspective on how some of these challenges could be overcome by using multi-agent modeling as a design framework within synthetic biology. Using case studies covering the construction of synthetic ecologies to biological computation and synthetic cellularity, we show how multi-agent modeling can capture the core features of complex multi-scale systems and provide novel insights into the underlying mechanisms which guide emergent functionalities across scales. The ability to unravel design rules underpinning these behaviors offers a means to take synthetic biology beyond single molecules or cells and toward the creation of systems with functions that can only emerge from collectives at multiple scales

Cardiovascular imaging 2011 in the International Journal of Cardiovascular Imaging

Cardiovascular Aspects of Radiolog

Determinants of renal oxygen metabolism during low Na+ diet : effect of angiotensin II AT1 and aldosterone receptor blockade

Reducing Na(+)intake reduces the partial pressure of oxygen in the renal cortex and activates the renin-angiotensin-aldosterone system. In the absence of high blood pressure, these consequences of dietary Na(+)reduction may be detrimental for the kidney. In a normotensive animal experimental model, reducing Na(+)intake for 2 weeks increased renal oxygen consumption, which was normalized by mineralocorticoid receptor blockade. Furthermore, blockade of the angiotensin II AT(1)receptor restored cortical partial pressure of oxygen by improving oxygen delivery. This shows that increased activity of the renin-angiotensin-aldosterone system contributes to increased oxygen metabolism in the kidney after 2 weeks of a low Na(+)diet. The results provide insights into dietary Na(+)restriction in the absence of high blood pressure, and its consequences for the kidney. Reduced Na(+)intake reduces thePO2(partial pressure of oxygen) in the renal cortex. Upon reduced Na(+)intake, reabsorption along the nephron is adjusted with activation of the renin-angiotensin-aldosterone system (RAAS). Thus, we studied the effect of reduced Na(+)intake on renal oxygen homeostasis and function in rats, and the impact of intrarenal angiotensin II AT(1)receptor blockade using candesartan and mineralocorticoid receptor blockade using canrenoic acid potassium salt (CAP). Male Sprague-Dawley rats were fed standard rat chow containing normal (0.25%) and low (0.025%) Na(+)for 2 weeks. The animals were anaesthetized (thiobutabarbital 120 mg kg(-1)) and surgically prepared for kidney oxygen metabolism and function studies before and after acute intrarenal arterial infusion of candesartan (4.2 mu g kg(-1)) or intravenous infusion of CAP (20 mg kg(-1)). Baseline mean arterial pressure and renal blood flow were similar in both dietary groups. Fractional Na(+)excretion and cortical oxygen tension were lower and renal oxygen consumption was higher in low Na(+)groups. Neither candesartan nor CAP affected arterial pressure. Renal blood flow and cortical oxygen tension increased in both groups after candesartan in the low Na(+)group. Fractional Na(+)excretion was increased and oxygen consumption reduced in the low Na(+)group after CAP. These results suggest that blockade of angiotensin II AT(1)receptors has a major impact upon oxygen delivery during normal and low Na(+)conditions, while aldosterone receptors mainly affect oxygen metabolism following 2 weeks of a low Na(+)diet.List of authors in thesis manuscript: Daniela Patinha, Carla Carvalho, Patrick Persson, Liselotte Pihl, Julie O'Niell, Fredrik Palm</p