“Electrifying” Natural Tools for the Nanoworld
Project to pave way for MS, Alzheimer treatments, spinal cord repair
He is addicted to success – and is not too modest about it. After undergraduate and graduate education on electric/electronics at Ankara’s Bilkent and the Middle East Technical Universities, respectively, and a Ph.D. from Georgia Institute of Technology earned in record time, he has set up shop at Koç University in Istanbul, where he is stalking bigger game which is sure to bring bigger prizes – well, who knows, may be the biggest!
Already picked for a 1.8 million Euro research grant from the European Union’s European Research Council from among 3000-plus candidates, Professor Özgür Barış Akan and his bank of hand-picked assistants are working on an ambitious project, which aims at providing artificial communication channels for the nature’s blocked ones.
The five-year project is titled “MINERVA: Communication Theoretical Foundations of Nervous System Towards Bio-Inspired Nanonetworks and ICT-Inspired Neuro Treatment”. The science-speak translates for the lay as using the tools provided by the communications theory to offer treatments for such neurological disorders as Multiple Sclerosis (MS) or Alzheimer by substituting artificial channels of communication for the disrupted or clogged ones between brain cells (neurons).
Why the acronym MINERVA? In Roman (actually Etruscan) mythology, the goddess is born from the head of Jupiter, the top-ranking god in the pantheon, as the fulfillment of a complicated prophecy and hence has come to symbolise wisdom. And the young scientist, 37, aims to pry into the source of that wisdom.
The significance of the grant is more in its nature than the generous sum: It is provided to a single researcher without such attached strings as required international partnerships or mandatory collaborations which normally accompany EU research funding. Another prerequisite for applicants is that their research should be groundbreaking.
As for Akan’s, it indeed breaks a ground where no others dared tread so far: Modeling the molecular communications between neurons with a view to emulating them with the tools of the classical wireless communications. The boldness of the venture comes under stronger light when one considers that our most complex organ works through harmonious functioning of its cells – 100 billion of them! With 1000-to-10.000 links, or “synaptic connections” in neuroscience lore, of a single neuron to others, the connections add up to a mind-boggling 100 trillion or even 1 quadrillion! Although the envisioned model will be confined to multiple connections between, say, a few dozen at most, the complexity of the mechanisms, involving interactions between signal-delivering chemicals dubbed neurotransmitters, electrochemical reactions, electric “spikes” still makes the job challenging.
Challenges? But they are what that make the young scientist go. An internationally-acknowledged expert on wireless communications, his papers stud prestigious journals, mainly the IEEE Transactions, the flagship of the scientific publications on electric/electronics with its collection of specialized journals, one of whose editorship was entrusted to him recently.
Recounting to Kurious how he embarked on this untrodden path, he started – with customary tribute to Richard Feynman, the visionary physicists – with his debut with the nanoworld of MEMS (microelectro-mechanical systems) and NEMS (nanoelectro-mechanical systems with dimensions billionths of a meter).
“I said to myself, ‘these nano gadgets, they make incredible things; but all by themselves. Why not team them up?
“Now, for three people to do something together, there has to be communication between them; that’s the basic need. So, ‘how can we make these nanogadgets talk to each other?’ There were some studies, but none originating from the world of communications. We were going to be the first. We started from there.”
Then he reasoned that cells were actually machines of similar size and were communicating among themselves, using molecules, pheromones etc. So his interest shifted to molecular communications, but the team’s early work was mainly theoretical abstract studies focusing on mechanics of motion (Brownian or other) of molecules, the best way of coding information (digital or analogue) and the kinds of communications channels used.
Throwing his expertise and energy into the task, he started churning out paper after paper which made top publications of the field.
Then, the team decided to move closer to the real life and studied the communication between two heart muscle cells or cardiomyocytes via ion channels through which they exchange calcium, potassium, sodium ions etc. These gates open and close in step with voltage differences to control the contraction of the heart. If this transfer of information, which is comparable to an electrical signal, proceeds at a specific flow rate, the heart contracts at the same moment. “So, what’s the capacity of this channel, which is, for all that matters, is a communications channel? For, if information travels from one place to another with the energy, this is communication. So we modeled this channel.
“Why we did that? Because, if I understand the system involved in the transfer of the input from this cardiomyocyte to another one; and if I understand what kind of contraction occurs when what passes through, then maybe I can link the diseases which disrupt the contraction with a communication problem.
“Our first motivation was how to make nanogadgets communicate. Then we turned to nature where communication is done with molecules, and eventually we moved on to human body, which functions perfectly thanks to millions of years of evolution. Can we learn from there? So we said ‘let’s construct these models, then validate them mathematically, but with physiological data we sought from authoritative colleagues in the medical profession.
“And if we can see conformity between our models and the workings of the body systems, can we put the technologies current at the world of telecom in the hands of medical colleagues? The motivation slid to that.”
The human brain is thought to contain some 100 billion nerve cells (neurons) and about as many support cells named glia. Neurons are described as cells which can be electrically stimulated and can exchange information through complex electrochemical processes. Unlike other cells of the body (somatic cells), neurons do not multiply by dividing. Until recently, it was thought that neuron formation was completed in the fetus and no new ones were produced after birth. But new research has shown that limited numbers of new neurons may be produced even in adult brains. Each neuron is made up of a round body called “soma”, a single arm called “axon”, covered by protective sheaths called myelin, that extends from the body and can be thousands of times longer, and filamentary extensions called dendrites. A neuron transfers its signal to other neurons via the axon to the dendrites of other neurons through junctions called synapses. A synapse is actually a 20-nanometer sized cavity. When an electric pulse comes, the chemicals (neurotransmitter molecules) contained in vesicles at the tips of filaments at the end of axon jump to the receptors on the other neuron and its dendrites. Through this mechanism, each neuron is in electrochemical communication with 10.000 other neurons over synaptic connections estimated to number 100 trillion to 1 quadrillion.
Although the findings were published in top journals, Akan did not follow up, “Because I had already stuck my head into the fascinating world of neurons.” “I started working on our first model with another of my students. Electrical spikes travel along the axon. There is a synapse between two neurons and a pre-synaptic terminal between the synapse and the axon where the electrical spikes are transformed into vesicle release. These vesicles contain neurotransmitters which diffuse when prompted by the signal. What are the properties of that simple channel? We modeled this in our first paper, following the easy path, basing our model on inter-neuronal communication at the hippocampal region of mouse brain, which is one of the most studied regions in literature.”
The human brain is thought to contain some 100 billion nerve cells (neurons) and about as many support cells named glia. Neurons are described as cells which can be electrically stimulated and can exchange information through complex electrochemical processes. Unlike other cells of the body (somatic cells), neurons do not multiply by dividing. Until recently, it was thought that neuron formation was completed in the fetus and no new ones were produced after birth. But new research has shown that limited numbers of new neurons may be produced even in adult brains. Each neuron is made up of a round body called “soma”, a single arm called “axon”, covered by protective sheaths called myelin, that extends from the body and can be thousands of times longer, and filamentary extensions called dendrites. A neuron transfers its signal to other neurons via the axon to the dendrites of other neurons through junctions called synapses. A synapse is actually a 20-nanometer sized cavity. When an electric pulse comes, the chemicals (neurotransmitter molecules) contained in vesicles at the tips of filaments at the end of axon jump to the receptors on the other neuron and its dendrites. Through this mechanism, each neuron is in electrochemical communication with 10.000 other neurons over synaptic connections estimated to number 100 trillion to 1 quadrillion.
Model of that point-to-point connection between two individual neurons was too simple and not so realistic for Akan’s taste, since neurons have multi terminal connections with thousands of dendrites from other neurons linked to synapse. Again, he drew parallels with his classical wireless communications, where techniques like “channel equalisation” are employed to cope with the phenomenon of interference in wireless networks, which crops up when, say, 10 different computers link with Wi-Fi. And the same phenomenon appears in the brain when an “n” number of neurons connected to a synapse fires simultaneously. The new vector for studies led to another torrent of papers from the team.
Then, Prof. Akan “saw a new light” which illuminated the path to MINERVA and the ERC grant.
“We want to find treatments for certain neurological disorders; right? But this whole neural system in the brain is just communication. Nothing but communication. And 90 percent of disorders stem from disrupted communications. And we humans are well versed in the area of communications. Non-biological communications, that is. We solve all kinds of problems. There is a solid body (of know-how). The problem is, this body has not been applied to this (neuronal) side.”
For Akan, MS is nothing other than interference, which develops when, for instance, immune system attacks and eats away myelin sheaths which insulate axons, just as a non-conductive wrapping insulates the copper wire at the center of a co-axial cable. When the myelin sheath deteriorates, the spikes which fire in the axon scatter around.
The team then decided to leave interference aside to extend the modeling of point-to-point channels to all kinds of neurons, including the motor and sensory neurons, which, although studied extensively in medicine and physiology, were never taken up in the domain of electric/electronics. “Can we look at the neural system in terms of multi-terminal channels; can we look at it as a nanonetwork and calculate its dimensions, the flow rate over that network? We are doing this on the Internet”, he elaborates.
The pinnacle of the achievements, however, will be the construction of an artificial synapse with carbon nanotubes over the last two years of the project, Akan says. There have been studies on artificial synapses by other groups before, but they were trials with different materials mimicking synaptic behavior, he points out.
Amused with the media hype on the projected device, he sounds a note of caution: “Although the ultimate aim is the treatment of spinal cord injuries, there can’t be anything more absurd than saying ‘we are going to implant this to paralysed patients at the end of five years’”. The motivation for that was constructing a test bed which was not made before, on which both electrical and molecular nanocommunication can be tested. “Of course, treatment of spinal cord injuries is another major motivation. But even if we manage to make this artificial synapse, maybe we can launch another project, together with medical people, to develop it for practical use. For that, “I may start studying medicine as a freshman.”
But he has other unfinished work to complete before giving a serious thought to embarking on a radically different career. Molecular communication is just half of his current pursuits. Among other state-of-the-art projects he is engaged is a “beyond the line-of-sight communication” for Lockheed-Martin, to use evaporation on ocean surfaces as a waveguide. He is also working together with chief scientist Jack Winters of Lockheed-Martin, “a legend in our world”, on a capacity-boosting MIMO (Multiple Input,, Multiple Output” device. He and his “body” of students and assistants are also engaged on “an indoor femtocell to work on terahertz band for 5-G” and magneto-inductive underwater communication devices. “But this is another story!”