Lectures

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Dr. Sir J. Fraser Stoddart – The Nobel Prize in Chemistry 2016 Winner

Professor Sir J. Fraser Stoddart began his research at the University of Sheffield in the 1980s before becoming chair of organic chemistry at the University of Birmingham in 1991, and in 1997 moving to UCLA as the Winstein Professor. In 2002, he joined the California NanoSystems Institute, rising to director in 2007, and in 2008 joined Northwestern University as a Board of Trustees Professor, establishing a Mechanostereochemistry Group in Evanston, Illinois.

Stoddart performed much of his work at University of California, Los Angeles (UCLA) where his team produced a large-scale 'ultra-dense' memory device that stores information using controllable molecular switches. This is an important step toward the creation of molecular computers that are much smaller and potentially more powerful than today's silicon-based models. He also developed interlocked, self-assembling molecules called 'suitanes', named for their appearance like a limbed torso in a suit.

Stoddart's awards also include the Albert Einstein World of Science Award in 2007 and he was appointed a Knight Bachelor in 2007.

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Dr. A. James Hudspeth

Born and raised in Houston, Texas, Jim Hudspeth conducted undergraduate studies at Harvard College and received PhD and MD degrees from Harvard's Graduate School of Arts and Sciences and its Medical School. Following postdoctoral work at the Karolinska Hospital in Stockholm, Sweden, he served on the faculties of the California Institute of Technology, the University of California, San Francisco, and the University of Texas Southwestern Medical Center. After joining Howard Hughes Medical Institute, Jim moved to The Rockefeller University, where he is F. M. Kirby Professor. Dr. Hudspeth conducts research on hair cells, the sensory receptors of the inner ear. He and his colleagues are especially interested in the active process that sensitizes the ear, sharpens its frequency selectivity, and broadens its dynamic range. They also investigate the replacement of hair cells as a potential therapy for hearing loss. Jim is a member of the National Academy of Sciences, the American Academy of Arts and Sciences, and the American Philosophical Society.

Your Biological Hearing Aid

As the gateway to verbal communication, the sense of hearing is of enormous importance in our lives. Hearing commences with the capture of sound energy by hair cells, the ear's sensory receptors, which convert that energy into electrical signals that the brain can interpret. Uniquely among our sensory receptors, the hair cell is not a passive recipient of stimuli, but instead uses an active process to enhance its inputs. The active process amplifies acoustical stimuli, sharpens frequency selectivity, and broadens the range of audible sound intensities. When the active process becomes unstable, most normal ears can even emit sound! Dr. Hudspeth will discuss the ear's normal operation, the basis of the active process, and efforts to restore damaged hearing through the regeneration of hair cells.

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Dr. Alexander George Bateman

At EMBL-EBI dr. Bateman is responsible for molecular biology data resources such as UniProt, Pfam, InterPro and Rfam. His overall scientific goal is to classify and annotate all protein and non-coding RNA sequences completely and accurately. His research is concerned with investigating bacterial adhesins and also in identifying spurious protein sequences that contaminate protein sequence databases. He is a long-time advocate of Wikipedia for scientific content. He is also becoming increasingly concerned about his and the contribution of other scientists' activities to the climate crisis.

Structure Predictions Transform Protein Family Classification

Structural prediction models have come of age and are beginning to revolutionise molecular biology. In the recent CASP competition AlphaFold 2 showed accuracies close in many cases to crystal structures. Other methods such as trRosetta and RaptorX still give excellent models that are adequate for many applications. In this talk I will discuss how in collaboration with David Baker's group we released a large collection (>6,300) of structural models for Pfam families. We have begun to dig into this treasure trove to refine, define and classify protein domain families.

Pfam is a collection of over 19,000 protein families with multiple sequence alignments and profile-HMMs. Pfam is widely used to annotate genomes and metagenomes. Ideally Pfam families would correspond to structural domains or repeats found in protein structures. However, often the Pfam family was built before a structure was known. They may be truncated single domains or contain multiple domains. We find that protein structural models can be used to split large multidomain families. Structural models based on Pfam alignments have been less useful to correct truncated domains and these will require the creation of structural models of full length proteins. The structural models have also been instrumental in identifying which superfamilies many Pfam's should belong to. Thus the difference between protein sequence and protein structure classification is becoming smaller and may be unified within the coming few years.

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Dr. Armando Azua-Bustos

Originally coming from agriculture and enology, later got a formal background in Environmental Microbiology, applied to astrobiology, and more recently, biotechnology. Has extensive laboratory and field-work experience, and a vast expertise in the ecology and evolution of microorganisms of extremely dry environments (xerophiles).

In 2017 started working as a Scientific Researcher at the Centro de Astrobiología of CSIC. In 2018 won one of the prestigious Human Frontiers Science Program Grants, and also a grant from the Dubai Future Foundation.

In 2017 won one of the prestigious TED Fellowships (having given 4 TED talks up to date). His work has been the focus of 6 international documentaries (including National Geographic, video clip here) and more that 100 appearances in the international news (i.e., Scientific American, PBS, Newsweek, Forbes, etc.).

Searching for Life in the Atacama Desert, the Driest, Oldest and Most Martian Place on Earth

The Atacama Desert in northern Chile is by far the driest and oldest desert on Earth, showing a unique combination of environmental extremes which explain why the Atacama has been investigated as a Mars analog model for almost twenty years. In this talk I will share how it is to work in this magnificent desert, and the lessons learned on the limits of habitability of planet Earth.

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Dr. Charles Cockell

His research interests cover life in extreme environments, the habitability of extraterrestrial environments, and space biology, using laboratory, field, orbital and other space platforms to investigate fundamental and applied questions in microbiology. He currently sits on the science advisory committee of NASA's Center for the Utilization of Biological Engineering in Space (CUBES) and is co-director of the UK Centre for Astrobiology.

Microbes in Space: Looking for Life and Human Settlement

In this talk I'll discuss the power of the microbial world to help us search for life beyond Earth and to help us implement the human exploration and settlement of space. In particular, I'll discuss some recent experiments on the International Space Station to study the use of microbes to do 'biomining' - extracting economically useful elements from the Moon, Mars and asteroids.

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Dr. Daniel Angerhausen

Dr. Daniel Angerhausen is an Astrophysicist and Astrobiologist at the Institute for Particle Physics and Astrophysics (IPA) at the Physics Department of ETH Zurich. The former NASA and Center for Space and Habitability fellow is also founder and CEO of the Science and Tech Communication start-up 'Explainables', a diverse team of highly qualified young communicators from all over the globe. On his search for planets around other stars Daniel already flew five missions on the NASA airborne telescope SOFIA. Daniel is also mentor and science committee member of NASA Frontier Development Lab, an Artificial Intelligence/Machine Learning incubator tackling challenges in various fields of space sciences in collaboration with industry stakeholders such as Google Cloud, Nvidia or IBM. Daniel plays Sepaktakraw, an artistic footvolleyball game and competed several times at World Championships in South East Asia.

Aliens, Exoplanets and Astrobiology

In my presentation I will give a non-expert introduction to the multi-disciplinary field of Astrobiology and in particular the science of extrasolar planets, planets orbiting stars outside our Solar System. I will describe my various projects in this emerging field using the largest ground based telescopes, the 'flying telescope' SOFIA (Stratospheric Observatory for Infrared Astronomy), the CHEOPS and JWST space telescopes the LIFE (Large Interferometer for Exoplanets) mission that I am working on at ETH Zürich. I will describe how these scientific methods and future telescopes will - for the first time in history - enable us to systematically search for life in space in the next two decades.

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Dr. David Baker

David Baker is a Howard Hughes Medical Institute Investigator, a professor of biochemistry, and an adjunct professor of genome sciences, bioengineering, chemical engineering, computer science, and physics at the University of Washington. Dr. Baker has published over 550 research papers, been granted over 100 patents, and co-founded 17 companies. Sixty-eight of his mentees have gone on to independent faculty positions. Dr. Baker is a recipient of the Breakthrough Prize in Life Sciences and is a member of the National Academy of Sciences and the American Academy of Arts and Sciences.

The Coming of Age of De Novo Protein Design

Proteins mediate the critical processes of life and beautifully solve the challenges faced during the evolution of modern organisms. Our goal is to design a new generation of proteins that address current-day problems not faced during evolution. In contrast to traditional protein engineering efforts, which have focused on modifying naturally occurring proteins, we design new proteins from scratch based on Anfinsen's principle that proteins fold to their global free energy minimum. We compute amino acid sequences predicted to fold into proteins with new structures and functions, produce synthetic genes encoding these sequences, and characterize them experimentally. In this talk, I will describe the de novo design of SARS-CoV-2 candidate therapeutics, synthetic antagonists and agonists of cellular receptors, molecular machines, and recent advances in deep learning-based structure modeling and design.

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Dr. Edith Heard

Edith Heard obtained her PhD from the Imperial Cancer Research Fund, London. In 2001, she set up her group at the Institut Curie and in 2010 became Director of the Institute's Genetics and Developmental Biology Unit. Edith was appointed as a Professor of the Collège de France in 2012, holding the Chair of Epigenetics and Cellular Memory. In January 2019, Edith started as Director General of EMBL.

Edith's group was among the first to show that the epigenetic process of X-chromosome inactivation (XCI). Her current research focuses on understanding how chromatin and chromosome organisation participate in gene regulation.

Edith and her laboratory have been recognised by many prizes, most recently recently the L'Oréal-UNESCO For Women in Science International Award, the Hansen Family Award, the Karl Bonhoeffer Award, Inserm Grand Prix, the European Society for Human Genetics Award and the Prix René et Andrée Duquesne of la Ligue contre le cancer.

The Genetic and Epigenetic Regulation of X-Chromosome Inactivation in Female Mammals

X-chromosome inactivation during early female development is an essential epigenetic process that is required to achieve appropriate dosage for X-linked gene products. We are interested in understanding how the differential treatment of the two X chromosomes in the same nucleus is set up during development and how this differential expression is then maintained, or reversed in certain circumstances during development or in a disease context. The establishment of X inactivation involves the non-coding Xist RNA that triggers chromosome-wide chromatin re-organisation and gene silencing. Our lab has provided recent insights into the nature of these chromosome-wide changes, and the factors that induce them. These include the Xist-mediated recruitment of the SPEN protein to actively transcribed genes. SPEN triggers gene silencing and dampens expression of genes that escape XCI (Dossin et al, 2020). The loss of active chromatin marks as well as the global loss of topologically associating domains (TADs) are also early events during XCI (Collombet et al, 2020). I will present my lab's recent insights into the relationship between Xist RNA, RNA Pol II and chromatin, during the process of X-linked gene silencing and escape from XCI.

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Dr. Laura Bojarskaitė

Dr. Laura Bojarskaite is a neuroscientist at Oslo University. For the past 6 years she has been investigating sleep, glial cells called astrocytes and the importance of sleep for "brainwashing" i.e. removal of harmful toxins from the brain, a process that is crucial for the prevention of neurodegenerative diseases.

Laura's sleep research findings have been published in prestigious scientific journals such as Nature Communications and described in international popular science news portals such as Technology Networks and Neuroscience News and Research. Laura is also a yogi, bookworm and a very passionate science communicator!

Nightlife of the Stars of the Brain – Astrocytes

While neuronal circuits are indisputably considered to be the computational integrators of behavior, a complete understanding of the nervous system must also incorporate the surrounding glial cells.

Astroglial function is far beyond passive support of neuronal circuits. Astroglia inextricably influences neuronal physiology from early development through guidance and synaptic shaping, and through entire life by structural and trophic support, immune function and extracellular homeostasis. With such essential functions astroglia are consequential to many different behaviors in adult animals. Sleep is no exception.

Sleep regulation has historically been admitted as a task exclusively for neurons. Changes in other types of brain cells, such as astrocytes, across the sleep-wake cycle and their role in sleep regulation are comparatively unexplored. Understanding what molecular mechanisms and signaling pathways astrocytes employ during sleep, and how they influence sleep physiology and brain rhythms, is a central outstanding question in the field of sleep research. In my talk, I will discuss our findings where we for the first time ever described astrocytic signaling during natural sleep and showed that astrocytic activity during sleep is important to maintain uninterrupted slow wave sleep and to maintain proper brain rhythms during sleep, such as sleep spindles (Bojarskaite et al., Nat Comm, 2020).

Also, seminal studies from the last 10 years have demonstrated the importance of astrocytes in chaperoning brain extracellular fluid flow during sleep for clearing waste products accumulated in wakefulness in a process called glymphatic flow. In 2013 a follow-up study showed that the glymphatic system is almost exclusively active during sleep, and under certain types of anesthesia, but not in wakefulness. The regulation of glymphatic fluid flow and mechanisms that underlie its enhancement upon sleep are only rudimentarily understood. In my talk, I will also discuss our yet unpublished results regarding mechanisms that could underlie the enhancement of brain waste clearance during sleep.

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Dr. Giedrius Gasiūnas

Dr. Giedrius Gasiunas is Chief Scientific Officer, who leads R&D projects at CasZyme. He also is a senior researcher at the Institute of Biotechnology of Life Sciences Center, Vilnius University, and member of Young Academy of the Lithuanian Academy of Sciences. He obtained a PhD in Biochemistry at Prof. V. Siksnys laboratory (Institute of Biotechnology, Vilnius University) in 2012. During the PhD he studied the mechanism of Cas9 protein activity, demonstrating that it is the programmable RNA guided DNA endonuclease. Giedrius Gasiunas is a co-author of 28 scientific publications, which are cited more than 3150 times and was involved in several Cas9 related patent applications.

Harnessing the Diversity of CRISPR-Cas Proteins for Genome Editing

The Cas9 protein from CRISPR-Cas bacterial defense systems has been adopted as a robust and versatile genome editing tool. However, for Cas9 to bind a given target, a short nucleotide sequence, termed protospacer adjacent motif (PAM), is required. This PAM constraint as well as insufficient specificity are major obstacles for Cas9 genome editing. Natural variation afforded by CRISPR-associated (Cas) enzymes provides a rich resource for the development of RNA-guided tools with diverse and potentially beneficial properties. To explore this largely uncharacterized diversity of the Class2 nucleases for genome editing applications, we applied cell-free biochemical screens to assess DNA cleavage requirements of nearly 80 Cas9 orthologues of Type II family and Cas-beta proteins from novel type V family. We show that this set of programmable nucleases demonstrate a wide range of activities in vitro and in cellular environment. Our results indicate that the natural diversity of Cas proteins provide a source of novel gene editing tools.

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Dr. Michal Schwartz

She is the world pioneer in breaking the long-held dogma regarding the relationships between the central nervous system and the immune system. Schwartz was the first to discover (1998) that blood-borne macrophages are needed for brain repair and the unexpected fundamental role of the immune system in supporting life-long brain functional plasticity and neurogenesis. Deciphering the mechanism led her to propose that aging or exhaustion of the immune system plays a key role in perpetuating Alzheimer's disease (AD) and dementia, and to suggest a novel treatment for AD, which harnesses the immune system to help the brain. The treatment approach is under expedited development towards the first-in-human trial, supported by an award from the Alzheimer's Association with the Gates Foundation.

The Two Decades That Revolutionized Brain Immunity: Implications for Immunotherapy to Defeat Alzheimer's Disease

For decades, the brain was considered an immune privileged organ, and as such, completely isolated from the immune system. Likewise, debilitating cognitive diseases were viewed as solely diseases of the brain, and specifically, as neuronal centric. With the discovery that the brain needs immune cells for its maintenance and repair, and the subsequent finding of niches within the brain's borders that host immune cells, we have attained a new understanding of brain-immune relationships. Accordingly, we proposed that systemic immune aging impacts brain aging and speed of progression of neurodegenerative diseases, even if not the primary cause of any of these conditions. We further demonstrated that the choroid plexus epithelium, anatomically and functionally connecting the circulation and the brain, critically affects the brain's fate in aging and neurodegenerative diseases. Accordingly, we proposed harnessing the body's immune system as a novel target for defeating AD and Tauopathy. Specifically, we showed that reducing peripheral immune system exhaustion by blocking inhibitory immune checkpoints triggers a cascade of immunological events that activate a common mechanism of repair, regardless of the primary cause of the disease. Such activation, leads within the brain, to reduction in toxic misfolded proteins, reduced inflammation, rescue of neurons, and arrest of cognitive loss. We found that this approach is dependent on bone marrow-derived macrophages, and has the potential to overcome Trem2 polymorphism. The path towards translating this approach for therapies leading to disease modification will be described.

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Dr. Regina Barzilay

Regina Barzilay is a School of Engineering Distinguished Professor for AI and Health in the Department of Electrical Engineering and Computer Science and a member of the Computer Science and Artificial Intelligence Laboratory at the Massachusetts Institute of Technology. She is an AI faculty lead for Jameel Clinic, an MIT center for Machine Learning in Health. Her research interests are in natural language processing and applications of deep learning to chemistry and oncology. She is a recipient of various awards including the NSF Career Award, the MIT Technology Review TR-35 Award, Microsoft Faculty Fellowship and several Best Paper Awards at NAACL and ACL. In 2017, she received a MacArthur fellowship, an ACL fellowship and an AAAI fellowship. In 2021, she was awarded the AAAI Squirrel AI Award for Artificial Intelligence for the Benefit of Humanity, the AACC Wallace H. Coulter Lectureship Award, and the UNESCO/Netexplo Award. She received her PhD in Computer Science from Columbia University, and spent a year as a postdoc at Cornell University. Prof. Barzilay received her undergraduate degree from Ben-Gurion University of the Negev, Israel.

Modeling Chemistry for Drug Discovery: Current State and Unsolved Challenges

Until today, all the available therapeutics are designed by human experts, with no help from AI tools. This reliance on human knowledge and dependence on large-scale experimentations result in prohibitive development cost and high failure rate. Recent developments in machine learning algorithms for molecular modeling aim to transform this field. In my talk, I will present state-of-the-art approaches for property prediction and de-novo molecular generation, describing their use in drug design. In addition, I will highlight unsolved algorithmic questions in this field, including confidence estimation, pretraining, and deficiencies in learned molecular representations.

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Dr. Richard James Youle

Dr. Youle received an A.B. degree from Albion College and his Ph.D. degree from the University of South Carolina where he worked on the protein toxin ricin. He joined the lab of David Neville at the National Institute of Mental Health for postdoctoral work on engineering new cell-type-specific protein toxins. He joined the Surgical Neurology Branch of NINDS in 1985 as a principal investigator where he has developed and moved into clinical trials new treatment strategies for brain tumors. His lab subsequently explored the molecular mechanisms of programmed cell death showing how Bcl-2 family members participate with mitochondria to control cell survival. Most recently his lab has discovered functions and interrelationships among proteins mutated in familial Parkinson's disease. His current work focuses on molecular mechanisms of autophagy, mitochondrial quality control and neurodegenerative disorders.

PINK1- And Parkin-Mediated Mitophagy in Neurodegeneration

PINK1 and Parkin, both mutated in familial PD, normally work intimately together to initiate autophagy of impaired mitochondria. When mitochondria are damaged, Pink1 senses the damage and accumulates specifically on the outer membrane of damaged mitochondria where it phosphorylates ubiquitin chains. These phosphorylated ubiquitin chains on the outer mitochondrial membrane bind to cytosolic Parkin and activate Parkin's E3 ubiquitin ligase activity yielding a feedback amplification loop that leads to autophagy of individual damaged mitochondria. Downstream of Parkin the machinery that mediates autophagosome recognition of damaged mitochondria links this pathway to genes mutated in ALS. Optineurin and the kinase TBK1, both mutated in familial ALS cases, participate in mitophagy in addition to NDP52. Optineurin and NDP52 bind to ubiquitin chains on mitochondria and also recruit autophagy machinery proteins, including the upstream kinase Ulk1 and the downstream autophagosome marker, LC3, to induce engulfment of the damaged mitochondria. NDP52 binds and recruits Ulk1 complex to initiate autophagosome biogenesis proximal to damaged mitochondria. Interestingly, in a murine model of exhaustive exercise, the product of the kinase PINK1 (phospho-S65 ubiquitin) is increased in the heart and this requires both endogenous PINK1 and Parkin expression representing a biomarker of PINK1 activity. Strategies to increase mitophagy as a defense against Parkinson's disease will be discussed.