Designing life with artificial intelligence

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“Designing Life with AI” is a cross-disciplinary MAKE project in which EPFL students get a chance to explore the research process by designing proteins. A total of eight research labs are involved.

Our body has some 20,000 different kinds of proteins: collagen, insulin, hemoglobin and many more. These molecules perform the myriad functions that are essential for our cells to survive. Thanks to advances in artificial intelligence, scientists are gaining valuable insight into the world of proteins and their various structures. Each protein has its own 3D structure that is associated with its function. Today, scientists can model these structures based on the amino acids sequences, and they can create new proteins designed for specific functions. All this opens up promising avenues of research in the field of protein design. This is the research opportunity that Sahand Jamal Rahi, an assistant professor and the head of EPFL’s Laboratory of the Physics of Biological Systems, wanted to give EPFL students through the project “Designing Life with AI”.

Get hands-on experience in research

“When I saw that AI-driven software was available for designing proteins in a fairly easy way, I realized I could combine my interest in the topic with my goal of giving more students experience with the research process,” says Rahi. “I’ve always encouraged students – especially those in my first-year thermodynamics class – to join EPFL research labs. I think it’s extremely valuable for young people to get hands-on experience in research, since reading about research is one thing, but applying it in practice is quite another.”

“Designing Life with AI”, which is supported by EPFL’s MAKE initiative, gives students the opportunity to carry out research projects involving protein design. Eight research labs and around 30 people are currently involved. Cris Darbellay and Mateo Schärer Gonzalez, bachelor’s students in life science engineering, are the project leaders for “Designing Life with AI”. They explain: “Beyond the research itself, students also get a chance to meet with professors and network informally. We also provide procedures for the lab experiments and user guides for the software.”

“When I saw that AI-driven software was available for designing proteins in a fairly easy way, I realized I could combine my interest in the topic with my goal of giving more students experience with the research process.”

– Sahand Jamal Rahi, a tenure-track assistant professor and the head of EPFL’s Laboratory of the Physics of Biological Systems

Creating proteins for specific purposes

The project that Gonzalez and Darbellay are working on relates to signaling proteins such as kinases, which play a key role in regulating cell function. They’re studying how light-oxygen-voltage-sensing domains (LOV domains) can be added to these proteins in order to regulate their activity. When LOV domains are exposed to blue light, for example, they change shape and can alter the protein’s state. “We’d ideally like to create a kinase that contains a LOV domain, so that the kinase can be activated by applying blue light,” says Darbellay.

Other “Designing Life with AI” projects relate to binders, compounds that can bind to specific proteins. Scientists use binders to identify a particular toxin, for example, block a protein or change a protein’s signaling pathways. Alexia Möller, a master’s student in life science engineering, and Dario Sergo, a master’s student in physics, are working on nanobodies, which are small fragments of antibodies. The two students are developing a fluorescent nanobody that uses a self-penetrating peptide to enter into cells. Their mechanism would enable scientists to observe protein interactions within human cells. “Our goal is to create a method for designing nanobodies that are tailored to individual antigens,” says Möller.

Proteins are central to the biological processes that support life. Breakthroughs in the study of proteins have applications in an array of areas, from disease detection and treatment to environmental remediation and carbon capture. At EPFL, a growing number of students are taking an interest in the vast potential of these fascinating molecules.

References
This article was first published in Dimensions, an EPFL magazine that showcases cutting-edge research through a series of in-depth articles, interviews, portraits and news highlights. Published four times a year in both English and French, it can be sent to anyone who wants to subscribe as well as contributing members of the EPFL Alumni Club. It is also distributed free of charge on EPFL’s campuses.

Author: Laureline Duvillard

Source: EPFL

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EPFL researchers create an AI model that thinks like we do

An EPFL team has created a new Large Language Model that is structured similarly to a human brain, allowing users more control and moving away from “black box” AI.

When a standard Large Language Model (LLM) is confronted with a problem, it tries to solve it by matching it to similar information it has seen before, and then give an answer based on those past patterns. But how it decides which information to use and what value it gives to different pieces of information can be somewhat inscrutable from the outside.

The LLM MiCRo (Mixture of Cognitive Reasoners) is architecturally divided into four specialized areas that act like different parts of the human brain, allowing users to have more control over how it approaches a question, and to better understand how it comes to its answers. The model, which was presented at the International Conference on Learning Representations, comes from the NLP Lab, part of the School of Computer and Communication Sciences (IC), and the NeuroAI Lab, part of IC and the School of Life Sciences at EPFL.

The four experts

To create MiCRo, researchers identified four regions of the brains specializing in different functions, which they call ‘experts’: language, logic, social reasoning, and world knowledge.

“The brain is organized into specialized regions, each tuned to handle a specific function. So far, we don’t see this division of labor as clearly in current language models,” says Badr AlKhamissi, a PhD candidate leading this research. “We picked four brain regions that neuroscientists know well and gave the model its own specialized modules, each one trained to be analogous to one of those brain regions.”

An LLM usually functions as a stack of layers that a problem or question can be processed through. In the case of MiCRo, each layer is divided into the four different experts. You give a sentence to the model starting at layer one, for example “The cat is asleep”. Then within this layer, the router can choose one expert for the first word “the”, but a different epxert for second word “cat” and so on, making it modular and highly adaptable.

“Each word of a sentence can go to different experts,” AlKhamissi explains. “So one sentence can actually be processed by multiple experts at each layer.”

Consider a prompt like: “Emma wants to split a CHF 60 dinner bill among three friends, but she knows that Jake lost his job last week and is too proud to say he’s struggling.” A purely mathematical module handles the arithmetic: CHF 60 divided by three is CHF 20 each. But the social reasoning module picks up on something subtler: Emma’s awareness of Jake’s situation, his unspoken pride, and the implicit suggestion that she might quietly cover his share. Both kinds of reasoning are needed to fully understand what’s going on, and in MiCRo, each aspect of the prompt is routed to the expert best equipped to handle it.

“When we see how the model works, we can see that it routes the words that relate to the social aspects to the social expert, and when it does the mathematical part, it routes those numbers to the logic expert.”

This separation makes it easier to see how the model is ‘thinking’ and why it makes certain decisions. It also means decisions can be steered – for example, you can decide to increase the impact of the social expert, or suppress the logic expert, depending on what kind of model you want to use in a certain situation.

“In traditional LLMs, you can do this via prompting by telling the model to make the output more social or make it more related to emotions,” AlKhamissi says. “But here, this is done by intervening in the architecture itself without doing any prompting.”

“A virtuous circle”

To create MiCRo, the EPFL team worked with Greta Tuckute, a neuroscientist from Harvard and MIT, to understand which parts of the human brain are activated by different problems, and then applied that learning to the model.

To identify the region analogous to the ‘logic’ expert in the brain, neuroscientists give humans demanding tasks, such as hard mathematical equations, and less demanding tasks, like easy mathematical equations, and then recorded their brain activity to find which brain regions are the most active for the demanding tasks versus non-demanding tasks. AlKhamissi’s team then did the same for the model, giving it demanding mathematical equations to see which experts would be most activated.

“The cool thing is we just used exactly what they do in neuroscience, but in the model. And the model was able to identify those experts on its own.”

While neuroscience informs the model, the model also informs the understanding of the brain, potentially allowing neuroscientists to discover the contributions of different areas for a given problem or question; for example that a certain sentence activates the language areas 20%, the mathematical areas 50%, and the social reasoning areas 40%.

“For my PhD work, I have been interested in this virtuous circle between neuroscience and AI. In one direction, we use findings and insights from neuroscience about the brain and integrate them into language models,” AlKhamissi says, “and now, with models like MiCRo, we can explore the other direction and ask how we can use AI models to help us understand the brain in a better way.”

Author: Stephanie Parker
Source: EPFL

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