Giant Jamboree 2014 , Hynes Convention Center, Boston MA iGEM Team of - PowerPoint PPT Presentation

Giant Jamboree 2014 , Hynes Convention Center, Boston MA iGEM Team of Ben-Gurion University, Be'er-Sheva, Israel

The e Met etaboli bolic c Syndrom drome Intro The Metabolic Syndrome What is it? Current treatment High Goals Diabetes Plasma Type 2 Triglycerides Strategies Policy & Abdominal Obesity Practices Low HDL (good) Hyperglycemia Cholesterol Fatty liver High blood Insulin pressure resistance

Some e Facts Intro The Metabolic Syndrome What is it? Health thy y lifest estyle yle: Current treatment • Appropriate dietary Goals • Routine exercise • Well sleeping Strategies Policy & Practices Lower risk for Metabolic Syndrome

Quick Quiz Intro The Metabolic Syndrome What is it? Current treatment 34% 34 • Sweet beverages Goals Strategies • High-fat food Policy & Practices • Not enough exercising 60 60%

Intro The Metabolic Syndrome What is it? Current treatment Goals Healthy lifestyle Strategies Policy & Practices

Curre rrent nt Treatmen eatment Intro The Metabolic Syndrome What is it? • Treating the symptoms rather Current Treatme ment than the causing factors Goals • Inefficient overall treatment Strategies • Conflicting side effects Policy & Practices

The e Vision on Intro The Less people suffering from Metabolic Syndrome the metabolic syndrome Goals ls Goal als: Strategies 1) Create synergetic multifunctional treatment Policy & Practices 2) Raise awareness in population at risk

Amon ong g Our Con onsultan sultants ts Intro The Metabolic Syndrome • Prof . Jaco cob Bar-Ta Tana, MD Metabolic Syndrome expert Goals ls • Prof . Assaf af Rudi udich ch, MD Strategies Endocrinologist, Diabetes expert Policy & Practices

The e Target rget Elem ements ts Intro The Metabolic Syndrome Goals ls Strategies Policy & Practices Fatty acid Insulin accumulation resistance in the liver

Intro The Metabolic Syndrome Goals Fatty acid Insulin accumulation resistance in the liver Strategies Policy & Practices 1 “Aspiration Shift” “Intelligent 3 Medication” “Artificial Exercise” 2

Fatty ty Liver Intro The Metabolic Syndrome • Non – adipose fat accumulation Goals • Fatty liver is highly correlated with the Metabolic Syndrome Strategies Policy & • We will treat Fatty Liver! Practices

“Artificial Exercise” Intro The Metabolic Syndrome Goals Strategies Artif ific icia ial l Exercis ise Aspiration Shift Intelligent Medication Policy & Practices

“Artificial Exercise” Intro The Metabolic Syndrome Goals DNP - 1930 ’s dietary aid: Strategies Uncoupling factor • Artif ific icia ial l Exercis ise Aspiration Shift Intelligent Medication Increasing oxidative • Policy & Practices phosphorylation

“Artificial Exercise” Intro The Metabolic Syndrome Goals DNP - 1930 ’s dietary aid: Strategies Effective • Artif ific icia ial l Exercis ise for losing weight Aspiration Shift Intelligent Medication Policy & Practices Side effect – • heating production

Mechani Me nism sm Intro The “Artificial Exercise” Metabolic Syndrome Goals Strategies Artif ific icia ial l Exercis ise Aspiration Shift Intelligent Medication Policy & Practices

Res esults ts Intro The “Artificial Exercise” Metabolic Syndrome Goals 10 nM TMRM 10 nM TMRM Strategies Artif ific icia ial l Exercis ise Aspiration Shift 25 nM TMRM 25 nM TMRM Intelligent Medication Policy & Practices Normal al HepG2 pcDNA3.1 UCP UCP1 No stain HepG2 - Human Hepatocarcinoma cell line

Intro “Aspiration Shift” The Metabolic Syndrome Indi dire rect ctly increasing Goals of fatty acid oxidation Strategies Artificial Exercise Aspira iratio ion Shift • Encouraging lipid transport Intelligent Medication Policy & • Mitochondrial biogenesis Practices Stop p storing ing and d start rt burning! ing!

Me Mechani nism sm Intro The “Aspiration Shift” Metabolic Syndrome Goals Strategies Artificial Exercise Fatty acid Aspira iratio ion Shift oxidation Intelligent Medication Policy & Practices

Modeling Mo ling Intro The Metabolic “Aspiration Shift” Syndrome Goals Goal: Validating the pers rson onaliz alized ed behavior Strategies of the treatment Artificial Exercise Aspira iratio ion Shift Intelligent Medication Methods ds & T Tools Policy & Practices

Intro The Metabolic Syndrome Model del Goals Resul sults ts Strategies Artificial Exercise Aspira iratio ion Shift Intelligent Medication Policy & Practices The model predicts: “Aspiration Shift” is a self-regulating personalized treatment

Insuli lin n Resist stance ance Intro The Metabolic Syndrome Goals Glucose absorption Insulin Strategies Artificial Exercise Aspiration Shift Insulin Intell llig igent Medi dicatio ion Glucose absorption resistance Policy & Practices Insulin resistance Hyperglycemia in the liver

Intro “Intelligent Medication” The Metabolic Syndrome Goals Current nt treatmen tment: t: High dose injection of insulin • Strategies Artificial Exercise Aspiration Shift Intell llig igent Medi dicatio ion Disadva vant ntages: Policy & Practices Inefficient • Uncontrolled • Non-specific •

Mechani Me nism sm Intro The “Intelligent Medication” Metabolic Syndrome Goals Targeted Delivery? Strategies Artificial Exercise Aspiration Shift Intell llig igent Medi dicatio ion Policy & Practices Based on “Conditional Dicer Substrate Formation via Shape and Sequence Transduction with Small Conditional RNAs ” ( Hochrein, Schwarzkopf, Shahgholi, Yin, & Pierce, 2013)

scRNA NA Constru tructo ctor Intro The “Intelligent Medication” Metabolic Syndrome OFF state ON state Goals Strategies Artificial Exercise Aspiration Shift Intell llig igent Medi dicatio ion Policy & Practices Produced by Nupack.org

Proof Pr f of C f Concept ept Intro The “Intelligent Medication” Metabolic Syndrome Goals Trigger Gene: mRuby2 Silencing Target Gene: eGFP FP Strategies Artificial Exercise Aspiration Shift mRuby2 eGFP+mRuby2 eGFP Intell llig igent Medi dicatio ion Policy & Practices

Pr Proof f of C f Concept ept Intro The “Intelligent Medication” Metabolic Syndrome Goals eGFP mRNA expre ression profi file 100.0 ls ion levels Strategies s) ted cells) 80.0 ssion Artificial Exercise mRNA express (vs. untreate 60.0 Aspiration Shift Intell llig igent Medi dicatio ion 40.0 44.4 38.2 Policy & 20.0 Practices 0.0 scRNA hairpin siRNA positive control Our specially designed hairpin reduced the expression of eGFP by 56 56%!

Mu Multicom compl plexit exity Treatment ment Intro The Metabolic Syndrome “Artificial Exercise” Goals • Evaluation of UCP1 functionality “Aspiration Shift” Strategies • Mathematical verification of the personalized Policy & Practices behavior “Intelligent Medication” • scRNA constructor software • Verification of the scRNA hairpin functionality

Research Policy & Practices

Intro The Metabolic Syndrome Goals Strategies Policy & Practices CEO of the Israeli Diabetes Association

Intro The Bedou ouin ins The Metabolic Syndrome Goals Strategies Policy & Practices

Intro The Bedou ouin in Campaign gn The Metabolic Syndrome 1) Raise awareness 2) Increase prevention behaviors Goals 3) Spread the vision of synthetic biology treatment Strategies Policy & Practices Dr . Younes Abu Rabia, MD

Metab tabolic lic Intro Amb mbas assadors sadors The Metabolic קילובטמ רודסבמא(הנומת )עוריאהמ Syndrome - הרטמ: ליצהל תטיקנו תועדומ תאלעה ידי לע םייח Aims: Goals הלועפ • Raising awareness - םימדקתמ םילופיטל עקרקה תא חינהל Strategies • Set the ground for advanced therapy - ירפסמ רואית – תופתתשה40 םיטנדוטס Policy & ו האופרה תועוצקממ5 םיעצוקמ םירבוד Achievements: Practices • 40 students participation • 5 professional speakers supporting the idea • Participation and honor certificates

Scholar olarsh ship ips Intro The Metabolic Syndrome • Bedouin student will Goals establish a new branch of the Israeli Diabetes תוגלמ Strategies Association in Rahat Policy & • 8 Bedouin students will Practices volunteer in diabetes clinics of their communities תחקל תוגלמ איבמ רוטקוד רניא לש הנומת up to 70 70% tuition on! ןורילמ