Mapping the Human Immune System

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University of Arizona research assistant professor and immunologist Adam Buntzman has harnessed supercomputers to map the human immune system for the first time. Bunztman will discuss his groundbreaking research using the CyVerse computing system, a system based at the U of A to provide computational infrastructure for big data problems in the life sciences.

TED SIMONS: A UNIVERSITY OF ARIZONA ASSISTANT PROFESSOR AND IMMUNOLOGIST HAS CREATED THE FIRST MAP OF THE HUMAN IMMUNE SYSTEM. ADAM BUNTZMAN CONDUCTED HIS GROUNDBREAKING RESEARCH USING SUPERCOMPUTERS FOR DATA SHARING AND ANALYSIS. HERE TO EXPLAIN WHAT THAT ALL MEANS FOR HEALTH AND SCIENCE IS THE U OF A'S ADAM BUNTZMAN. WELCOME TO "ARIZONA HORIZON." THANKS FOR COMING UP TO TALK TO US. THIS IS FASCINATING TO ME. I WANT YOU TO EXPLAIN IT FOR ALL OF US. IT REALLY SOUNDS LIKE -- MAPPING THE HUMAN IMMUNE SYSTEM. WHAT ARE WE TALKING ABOUT HERE?

ADAM BUNTZMAN: IMMUNOLOGISTS THINK ABOUT THE IMMUNE SYSTEM IN A COUPLE OF WAYS. AN EASY WAY TO THINK ABOUT IT IS IT'S BROKEN INTO TWO PARTS. ONE PART OF THE IMMUNE SYSTEM IS CALLED THE INNATE IMMUNE SYSTEM WHERE YOU HAVE A SERIES OF RECEPTORS THAT BIND TO THINGS LIKE MICROBES THAT WE ENCOUNTER EVERY DAY. WE'RE INUNDATED WITH BACTERIA AND FUNGI AND OTHER PATHOGENS. WE NEED TO BE ABLE TO SEE THEM AND DETECT THEM AS FOREIGN. THERE ARE SOME PARTS OF THOSE MICROBES, SOME PARTS OF THE VIRUS AND BACTERIA THAT WE CAN ACTUALLY DETECT -- THEY DON'T CHANGE VERY MUCH, AND WE KEEP THE SENSORS THAT DETECT THEM RELATIVELY STABLE IN OUR GENOME. THERE'S ANOTHER HALF OF THE IMMUNE SYSTEM CALLED ADAPTIVE IMMUNE SYSTEM. BECAUSE OF THIS ENORMOUS ARRAY OF MICROBES OUT IN THE ENVIRONMENT, WE NEED TO BE ABLE TO SEE NEW MICROBES WE'VE NEVER OBSERVED BEFORE, OUR BODY HAS TO DETECT THEM AND REMEMBER THEM AND BE ABLE TO CLEAR THAT MICROBE AND RESPOND MORE ROBUSTLY THE NEXT TIME IT'S OBSERVED BY THE BODY. THE ADAPTIVE IMMUNE SYSTEM IS WHAT WE'RE STUDYING NOW. THE PROBLEM IS THE GENES THAT CODE FOR THE ADAPTIVE IMMUNE SYSTEM ARE BROKEN GENES. THEY'RE LITTLE FRAGMENTED GENES THAT NEED TO BE PLACED BACK TOGETHER ACTUALLY. THESE ARE GENES THAT FUNCTION IN THE WHITE BLOOD CELLS OF YOUR BODY. THEY'RE B CELLS OR T CELLS AND MAKE TWO MOLECULES. ANTIBODIES AND T-CELL RECEPTORS. WHEN THEY'RE PLACED BACK TOGETHER TO MAKE A FUNCTIONAL ONE, THEY DO SO IN EACH INDIVIDUAL CELL, EACH INDIVIDUAL WHITE BLOOD CELL. WHEN THEY'RE GLUED BACK TOGETHER, THEY'RE GLUED BACK TOGETHER IN A MYRIAD OF WAYS. HUGE VAST NUMBERS OF WAYS. AT THE EDGES OF WHERE THESE GENES ARE GLUED BACK TOGETHER, THERE'S LITTLE TINY CHANGES. EACH TIME IT CHANGES, IT CAN DETECT A DIFFERENT VIRUS, A DIFFERENT BACTERIA. EACH CELL WILL HAVE ITS OWN UNIQUE CELL RECEPTOR.

TED SIMONS: YOU'VE MAPPED THE IMMUNE RECEPTORS AND MAPPING THEM THUSLY?

ADAM BUNTZMAN: THAT'S RIGHT. THE CONCEPT HERE IS THAT IT WAS ESSENTIALLY THOUGHT TO BE TOO LARGE OF A SYSTEM TO MAP. THERE'S PREDICTIONS THAT THE NUMBER OF WAYS YOU CAN MAKE ALL OF THESE IMMUNE RECEPTORS EXCEED TEN TO THE 18TH POWER. THAT'S A TRILLION TIMES A MILLION. AND SO THAT'S A VERY LARGE NUMBER, LARGER THAN PEOPLE TYPICALLY WORK WITH. OUR WHOLE GENOME IS THREE WITH NINE ZEROS. NOW YOU'RE TALKING ABOUT ONE LITTLE SET OF GENES THAT CAN BE REWORKED AND PLACED BACK TOGETHER IN SUCH A WAY TO CREATE THIS ENORMOUS VARIATION. THE PATTERNS OF WHICH HELP PROTECT YOU AND ME AGAINST INFLUENZA AND ALL THE DIFFERENT MICROBES WE FACE ON A DAILY BASIS. FINDING THOSE PATTERNS IN THOSE RECEPTORS IS KEY TO UNDERSTANDING HOW WE RESPOND UNIQUELY TO INFLUENZA AND HOW IT'S DIFFERENT TO OTHER MICROBES AND HOW WHEN OUR IMMUNE SYSTEM GOES AWRY, HOW WE RESPOND TO CANCER OR HOW OUR IMMUNE SYSTEM DEVELOPS INTO A CANCER OR CONTEXT ITSELF.

TED SIMONS: YOU'VE GOT ALL THIS INFORMATION. THERE'S A TON OF INFORMATION. WHAT IS CyVerse AND HOW DID THAT HELP YOU MAP THE IMMUNE SYSTEM?

ADAM BUNTZMAN: YES. CyVerse IS AT THE UNIVERSITY OF ARIZONA. IT IS A COMPUTATIONAL INFRASTRUCTURE. IT'S ESSENTIALLY A LARGE GROUP OF INDIVIDUALS WITH LARGE NATIONAL SCIENCE FOUNDATION FUNDING, AND THEIR JOB IS TO BE ABLE TO MAKE -- TO COLLECT COMPUTATIONAL TOOLS, COMPUTERS THEMSELVES, AND SOFTWARE THAT ALLOW BASIC SCIENCE BIOLOGISTS AND IMMUNOLOGISTS OR OTHER TYPE OF BIOLOGISTS TO USE COMPUTERS WHEN THEY DIDN'T NECESSARILY TRAIN THEIR ENTIRE LIVES TO DO SO. THERE ARE MANY RESEARCH FIELDS NOW HAVE TO USE VERY LARGE THROUGH PUT SEQUENCING TYPES OF TECHNIQUES WHERE THE DATA IS JUST TOO LARGE FOR THEM TO HANDLE. THEY NEED COMPUTERS TO BE ABLE TO HANDLE THEM BUT WITHOUT THE TRAINING WITH WHICH TO DO SO. THIS IS A METHOD OF BEING ABLE TO GENERATE BOTH THE PLACE TO FIND THE COMPUTERS AND COMPUTER SYSTEMS AND HUMAN BEINGS THAT WILL HELP YOU FACILITATE UTILIZING THOSE COMPUTERS. BECAUSE QUITE FRANKLY, IF YOU HAVE AN ENORMOUS COMPUTATIONAL SYSTEM WITHOUT THE ABILITY TO USE IT, YOU'RE IN TROUBLE.

TED SIMONS: SO YOUR RESEARCH TOOK HOW LONG?

ADAM BUNTZMAN: WELL, IT'S BEEN IN DEVELOPMENT APPROXIMATELY TEN YEARS. THIS MAPPING OF THE IMMUNE SYSTEM PORTION I DID IN COLLABORATION WITH A CyVerse RESEARCHER AND A MEMBER OF THE UNIVERSITY OF ARIZONA DEPARTMENT OF ENGINEERING COMPUTER AND ELECTRICAL ENGINEERING MUCH HIS NAME IS DR. ALI AKOGLU. TOGETHER WE DESIGNED AN ALGORITHM TO MAP HOW MANY DIFFERENT WAYS YOU CAN CREATE EACH ONE OF THESE ADAPTIVE IMMUNE RECEPTORS AND GENERATE A HUGE MAP OF THE LANDSCAPE OF THOSE IMMUNE RECEPTORS. NOW WE CAN SEQUENCE USING WHOLE GENOME SEQUENCING TOOLS. WE CAN SEQUENCE NOT THE WHOLE GENOME. WE FOCUS JUST ON THE RECEPTORS OF THE ADAPTIVE IMMUNE SYSTEM AND SEQUENCE EVERY SINGLE WHITE BLOOD CELL THAT MAKES EACH AND EVERY DIFFERENT IMMUNE RECEPTOR AND PLACE IT ON THIS ARCHITECTURE. THIS MAP MUCH THE HUMAN GENOME AND FIND OUT WHERE THE PATTERNS EXIST WHEN YOU RESPOND TO INFLUENZA WHICH RECEPTORS ARE YOU USING. WHEN THERE'S A SUCCESSFUL IMMUNE RESPONSE WHICH IMMUNE RECEPTORS YOU'RE USING AND HOW DOES THAT DIFFER FROM AN UNSUCCESSFUL IMMUNE RESPONSE.

TED SIMONS: THIS SUPERCOMPUTER MADE RESEARCH THAT WOULD HAVE TAKEN HOW LONG HOW LONG?

ADAM BUNTZMAN: WE MODELED DOING A VERY SMALL PROGRAM THAT WOULD HAVE DONE A LITTLE CHUNK OUT OF IT A LARGE CLUSTER OF CPUs, WE ESTIMATE IT WOULD HAVE TAKEN US OVER 106 YEARS TO COMPLETE THE MAPPING PROCESS. IT TOOK US 16 AND 2-THIRDS DAYS.

TED SIMONS: THAT'S UNBELIEVABLE. THAT'S FANTASTIC. IT SOUNDS LIKE ADAPTIVE IMMUNE SYSTEM -- IT SOUNDS LIKE YOU'RE ALMOST MOVING THE GOALPOSTS HERE A LITTLE BIT. WHAT DO WE TAKE FROM THIS? WHEN WILL THIS IMMUNOLOGY MAP -- WHEN WILL THIS BECOME A REAL SERVICE TO FOLKS?

ADAM BUNTZMAN: IT'S AT THE EDGE OF THAT RIGHT NOW. RIGHT NOW, WE ARE ACTIVELY UTILIZING IMMUNE SEQUENCING TO DETECT LYMPHOMA AND LEUKEMIAS. IT'S A HUNDRED FOLD MORE SENSITIVE THAN THE PRIOR TECHNIQUES HAVE BEEN. THOSE ARE NOW STARTING TO EKE INTO THE CLINICAL REALM, AND I THINK IT'LL BE REALLY ROBUSTLY WITHIN THE NEXT 1 TO 2 NEARS.

TED SIMONS: SO IT'S HAPPENING.

ADAM BUNTZMAN: YES.

TED SIMONS: THIS MUST BE QUITE A REWARD FOR YOU. CONGRATULATIONS AND CONTINUED SUCCESS. THANK YOU VERY MUCH FOR JOINING US.

ADAM BUNTZMAN: THANK YOU FOR HAVING ME.

Adam Buntzman,research assistant professor and immunologist, University of Arizona

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