The Biotech Futurist

Play: Chimpanzees, Bonobos, Uncertainty, Sex, Animal Societies

How about play in animals?
 
Today I have the pleasure to discuss outstanding research in ethology with Elisabetta Palagi from the University of Pisa, who has been a leader in Primatology for over 30 years, and, among several successes, was recently awarded the Animal Behavior Society Fellowship Award for her outstanding research.
 
In this episode, we explore animal play behavior, focusing on social play. We examine its definition and functions across different animal groups, gaining insights into its diverse manifestations. We delve into the methodologies used by ethologists to study play and its decline as animals mature. We discuss the paradoxical nature of play, its role in social competence development, and its significance among infant chimpanzees. Communication and rough-and-tumble play are explored, along with self-handicapping and the enduring importance of play in adulthood. We compare playfulness in bonobos and chimpanzees and investigate facial expressions and mimicry in play and sexual behavior. This journey unravels the evolutionary significance of play, communication dynamics, and its impact on social bonds in animal societies.
 
If you liked this episode, please consider subscribing to The Biotech Futurist on Spotify, Apple Podcast, Stitcher, Google Podcast, or your favorite platform, and leaving a positive review. The growth of this podcast depends critically on word-of-mouth. Thank you for your help. Follow The Biotech Futurist on Instagram and YouTube, and DM or email me if you have any curiosity. You can always download the transcript of this episode and find the links to the papers we mention on my website, lucafusarbassini.com. The jingle is by Gabriele Fusar Bassini. Elisabetta Palagi’s picture is by Luca Ragaini.
RESOURCES
[ACADEMIC] Rough-and-tumble play as a window on animal communication: https://onlinelibrary.wiley.com/doi/abs/10.1111/brv.12172#:~:text=ABSTRACT,of%20escalation%20to%20serious%20fighting.
[ACADEMIC] Not just for fun! Social play as a springboard for adult social competence in human and non-human primates: https://link.springer.com/article/10.1007/s00265-018-2506-6
[ACADEMIC] Mirror replication of sexual facial expressions increases the success of sexual contacts in bonobos: https://www.nature.com/articles/s41598-020-75790-3#:~:text=In%20bonobos%2C%20during%20sex%20RFM,%2D%20and%20hetero%2Dsexual%20interactions

Computers Now Know Gene Networks: Transfer Learning And Massive Single Cell Transcriptomes Predict Bio | Christina Theodoris

What if we had a ChatGPT for transcriptomics, what if we could predict how the gene network is changed in diseases for which we have scarce molecular data?
Today I have the immense pleasure to discuss transformers in single-cell transcriptomics to make huge predictions about gene modulation with Christina Theodoris, who today first-authored a paper in Nature entitled “Transfer learning enables predictions in network biology”. Christina has recently started her own lab at Gladstone Institutes to study gene networks with a focus on the heart and cardiovascular disease, after working at Harvard, the Broad, and Children’s.
Christina and I discuss in an entertaining and technical conversation her impressive model, GENEFORMER.  We introduce foundational concepts in machine learning that enabled her work: pre-training on large scale datasets and transfer learning followed by task-specific fine tuning, to democratize fundamental knowledge; rank value encodings; self-attention; masked learning objectives and self-supervision; embeddings. Christina pooled the huge amount of RNA-seq transcriptomic data generated worldwide at the single-cell level in recent years so to make a model that knows the gene-gene expression correlations, for all the cell types in the human body, and understands their gene networks so well that it can predict how they rewire and genes change expression when you perturb single genes or combinations of them. We discuss current applications, such as in silico reprogramming and differentiation, in silico deletion of genes or modeling of dosage reduction or increase for the study of haploinsufficiencies. Christina beautifully explains how such a fine-grained network view of single-cell biology can help us identify key genes to normalize by medical intervention to restore health in disease settings. Her model is powerful to understand the genome-wide, all-tissues expressive consequences of diseases for which only a limited amount of data is available, thanks to transfer learning, it can model the effect of treatments that modulate the expression of specific genes, and it is so promising for understanding in depth rare diseases and more, including cardiovascular diseases as shown in the first report. We end by speculating on the broad applicability of her model, and the possibilities of growth, for instance by integrating several omics data, towards the dream of generating entire virtual patients starting simply from their DNA sequence. I honestly can’t make predictions about what Christina and her colleagues will do in the next few years, as their GENEFORMER is completely out of what I thought was already coming!
If you liked this episode, please consider subscribing to The Biotech Futurist on Spotify, Apple Podcast, Stitcher, Google Podcast, or your favorite platform, and leaving a positive review. The growth of this podcast depends critically on word-of-mouth. Thank you for your help. Follow The Biotech Futurist on Instagram and YouTube, and DM me if you have any curiosity. You can always download the transcript of this episode and find the links to the papers we mention on my website, lucafusarbassini.com. The jingle is by Gabriele Fusar Bassini.
[ACADEMIC] “Attention is all you need”: https://proceedings.neurips.cc/paper/2017/file/3f5ee243547dee91fbd053c1c4a845aa-Paper.pdf
Christina’s lab: https://gladstone.org/people/christina-theodoris
[ACADEMIC] Transfer learning enables predictions in network biology: https://www.nature.com/articles/s41586-023-06139-9
 

Is It Possible To Predict Lifespan From A Biopsy? | Alessandro Cellerino

What if told you that your lifespan is probably predictable from a biopsy?
Today I have the pleasure to discuss state-of-the-art epigenetic clocks for biological age and lifespan estimation to develop interventions that slow down aging with my former mentor Professor Alessandro Cellerino. Prof Cellerino is a world leader in aging and longevity research. He is an Associate Professor and Research group leader at the Scuola Normale Superiore in Pisa and the Leibniz Institute on Aging.
Prof Cellerino and I discuss how he and his collaborators established quickly and with great success Nothobranchius furzeri, Killifish for friends, as a model organism for aging research, so to test pharmacological and non-pharmacological interventions with the hope to slow down or reverse the aging process. But this needs to measure aging and how fast it proceeds for different individuals, leading us to discuss epigenetic clocks, which might effectively predict your biological age from a simple biopsy from your skin! So if you happen to have a biological age which is more than your chronological age, take action, it means you are aging faster than your same-year old high-school peers! We discuss how striking the RNA-seq revolution has been also for the aging field, how conditions that result in faster or slower aging are probably often set early, much before the aging process begins. We analyze some of the common machine learning techniques employed by epigenetic clocks, and the difficulties to infer causality and identify crucial genes, as several different combinations of relatively few genes can all equally well predict biological age. Finally, we reason on the importance of multi-species clocks for translational research: clocks that work both in model organisms and in humans, such as the transcriptiomic clock just published by Ferrari et al. in the Cellerino Lab, which employs an innovative architecture to control for the effect of confounders such as sex on the age prediction. Looking forward to seeing what Prof Cellerino and the Cellerino lab achieve in the next few years!
If you liked this episode, please consider subscribing to The Biotech Futurist on Spotify, Apple Podcast, Stitcher, Google Podcast, or your favorite platform, and leaving a positive review. The growth of this podcast depends critically on word-of-mouth. Thank you for your help. Follow The Biotech Futurist on Instagram and YouTube, and DM or email me if you have any curiosity. You can always download the transcript of this episode and find the links to the papers we mention on my website, lucafusarbassini.com. The jingle is by Gabriele Fusar Bassini.
RESOURCES
[ACADEMIC – a great paper illustrating the role of the Nothobranchius furzeri “Killifish” in aging research] Longitudinal RNA-Seq Analysis of Vertebrate Aging Identifies Mitochondrial Complex I as a Small-Molecule-Sensitive Modifier of Lifespan: https://www.cell.com/fulltext/S2405-4712(16)30030-8
[ACADEMIC] A deep neural network provides an ultraprecise multi-tissue transcriptomic clock for the short-lived fish Nothobranchius furzeri and identifies predicitive genes translatable to human aging: https://www.biorxiv.org/content/10.1101/2022.11.26.517610v1
[ACADEMIC, foundational review on epigenetic clocks] DNA methylation-based biomarkers and the epigenetic clock theory of ageing: https://www.nature.com/articles/s41576-018-0004-3
The Cellerino Lab: https://www.leibniz-fli.de/research/associated-research-groups/cellerino/current-projects-and-team
 

Gene Editing Meets Nanomedicine: A Trustworthy Friendship? | Vittoria Raffa

What if gene editing went on a date with nanomedicine?
Today I am lucky to spend some time talking to my former mentor Vittoria Raffa about all the fundamental molecular biology of gene editing, and the open challenges to translate CRISPR-based technologies to the clinic. Will nanomedicine and synthetic biology be the right partners for gene editing to make it? Vittoria is an Associate Professor of Nanomedicine and Molecular Biology at the University of Pisa, and she’s been a leader in nanomedicine since a very young age.
Vittoria and I start from her experience as the coordinator of the European project I-GENE, which provides a great example to today’s episode, as it combines gene editing, nanomedicine, and synthetic biology concepts. The I-GENE Project is building, specifically, a light-switchable nanoformulation for gene editing, to be first used for melanoma. Vittoria and I discuss the main CRISPR-based technologies, including “traditional” editing with CRISPR/Cas9 and its natural and evolved or engineered variants, base editors, prime editors, PASTE editors, CRISPRa/i. We consider the main open challenges to broadly translate gene editing to the clinic: delivery, off-target toxicity, immunogenicity, cost, and more. Vittoria beautifully explains why the current number of 26 clinical trials, even if huge for how long ago this technology was invented, is less than what can be done: CRISPR-based gene editors are mostly delivered by viral vectors, which cost a lot to make. She suggests that the widespread deployment of nanomedical devices could greatly reduce the cost of therapies, hence accelerating the development of CRISPR medicines for more and more diseases, and at an affordable cost. She then guides us through recent concepts in synthetic biology, especially to build nanomedical tools that recognize multiple cellular inputs and release the drug, such as the gene editor, only when a number of logic gates turn true. I’ll stop here, there’s so much more to discover in our conversation! Looking forward to seeing what Vittoria and the Raffa lab achieve in the next few years!
If you liked this episode, please consider subscribing to The Biotech Futurist on Spotify, Apple Podcast, Stitcher, Google Podcast, or your favorite platform, and leaving a positive review. The growth of this podcast depends critically on word-of-mouth. Thank you for your help. Follow The Biotech Futurist on Instagram and YouTube, and DM me if you have any curiosity. You can always download the transcript of this episode and find the links to the papers we mention on my website, lucafusarbassini.com. The jingle is by Gabriele Fusar Bassini.
[ACADEMIC, outstanding review on most of the state of the gene editing field with a focus on medical applications] Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors: https://www.nature.com/articles/s41587-020-0561-9
[ACADEMIC REVIEW] CRISPR/Cas9 in the era of nanomedicine and synthetic biology: https://www.sciencedirect.com/science/article/pii/S1359644622003683
The I-GENE Project that Vittoria coordinates: https://i-geneproject.eu/
[OUTREACH] CRISPR clinical trials, 2022 Update by the Innovative Genomics Institute: https://innovativegenomics.org/news/crispr-clinical-trials-2022/
 

Industrial Biotech, SynBio, Yeasts, And Outreach | Stefano Bertacchi

What’s the revolution of synthetic biology and metabolic engineering in Industrial Biotech?
Welcome to the latest episode of The Biotech Futurist, where we drive around the fascinating field of industrial biotechnology. Today, I have the pleasure of interviewing Stefano Bertacchi, a passionate researcher and EU bioeconomy ambassador. Stefano shares with us his journey, from his interest in microorganisms and yeasts to his current research in industrial biotechnology.
Stefano introduces us to the main themes, goals, and research directions in the field of industrial biotechnology. We explore the biotech story behind everyday products that we tend to forget about and the contribution of biorefineries to sustainable and circular economies. We delve into lignocellulosic biomasses, which are interesting in a bioeconomy setting as a preferred feedstock for biorefineries. Stefano explains the concepts of separate hydrolysis and fermentation and simultaneous saccharification and fermentation, their timing, and the useful products that can be obtained.
We learn about bioreactors, their workings, and examples of Stefano's favorite microorganisms deployed by biorefineries. Stefano shares how they are discovered, optimized, engineered, and evolved, and the difference between adaptive laboratory evolution (ALE) and directed evolution. We discuss the microbial synthesis of organic acids as a key example of industrial biotech processes, evaluating different substrates, and building a new industrial biotechnology, taking into account the value chain, downstream purification, and testing small batches in academia.
Stefano also shares his views on the emerging and revolutionary role of synthetic biology and metabolic engineering. We explore Stefano's everyday life as a researcher in industrial biotech and his role as an EU bioeconomy ambassador and public figure in science outreach in Italy. Stefano finally shows us the power of memes for science communication.
If you liked this episode, please consider subscribing to The Biotech Futurist on Spotify, Apple Podcast, Stitcher, Google Podcast, or your favorite platform, and leaving a positive review. The growth of this podcast depends critically on word-of-mouth. Thank you for your help. Follow The Biotech Futurist on Instagram and YouTube, and DM or email me if you have any curiosity. You can always download the transcript of this episode and find the links to the papers we mention on my website, lucafusarbassini.com. The jingle is by Gabriele Fusar Bassini.
 

Ableism and Genetic Counseling [Bonus episode] | Jenna Pucel

I am delighted to host Jenna Pucel for a short bonus episode on ableism, a urgent topic in bioethics, strongly connected with this week's theme, genetic counseling. Excited to keep having conversations with Jenna and people like her!

A Day In The Life Of A Genetic Counselor: From Genetic Technologies To Ethics | Tori Suslovitch

What if we had non-directive, unbiased genetic counseling all over the world?
Today I have fun talking to Victoria (Tori) Suslovitch, friend and coworker from the Yu Lab in Boston. Tori is a genetic counselor, and she has been supporting the logistical, educational, and emotional needs of patients and families enrolled in translational genomics studies for a long time.
Tori and I try to give an exhaustive overview of the world of genetic counseling, starting from her daily experience in the world of interventional genomics for ultrarare diseases. Tori moves between history, definitions, technologies, ethics challenges, direct experiences, to show us how genetic counseling is really about empowering people with applied knowledge in genetics and psychological support to take decisions that follow their values and priorities when it comes to genetics, also in the light of the uncertainty of a continuously evolving genetic knowledge. This is now entering several fields, from genetic decisions in cancers, to prenatal testing, interventional genomic experimental therapeutics for ultrarare diseases,… Tori explains the process and the profession of the genetic counselor, and she cleverly remarks how currently we still have unbalanced genomic datasets, with Western people by far most represented, and how the field also needs more diversity within the profession. We also discuss a few case studies on the broader ethics of genomics, such as the Chinese babies edited with CRISPR/Cas9 by He Jiankui against all the scientific community, and the delicate balance of risks and benefits when new genes are added to prenatal tests. This field is moving at a rapid pace, and I am sure that if I ever interview Tori again in a few years, we’ll have so much new knowledge to unpack!
If you liked this episode, please consider subscribing to The Biotech Futurist on Spotify, Apple Podcast, Stitcher, Google Podcast, or your favorite platform, and leaving a positive review. The growth of this podcast depends critically on word-of-mouth. Thank you for your help. Follow The Biotech Futurist on Instagram and YouTube, and DM or email me if you have any curiosity. You can always download the transcript of this episode and find the links to the papers we mention on my website, lucafusarbassini.com. The jingle is by Gabriele Fusar Bassini.
RESOURCES:
National Society of Genetic Counselors: https://www.nsgc.org/
[OUTREACH] The DNA Exchange: https://thednaexchange.com/
“I am a Genetic Counselor”: A qualitative exploration of field leaders’ perceptions of the title “genetic counselor”: https://onlinelibrary.wiley.com/doi/abs/10.1002/jgc4.1184
[OUTREACH] Short, recent MIT commentary on the CRISPR babies scandal: https://www.technologyreview.com/2022/04/04/1048829/he-jiankui-prison-free-crispr-babies/

The Scientist Who Records The Computations Of Cells | Adam Cohen

What if we could record several molecular events happening inside cells along time?
Today I have the pleasure to discuss an outstanding tool to record molecular events in time with Professor Adam Cohen. Adam is a Professor of Chemistry, Chemical Biology, and Physics at Harvard, he has countless academic and extra-academic achievements that led to his MIT Technology Review nomination to the 35 world's top innovators under 35 in 2007. 
Adam and I chat about Adam’s story as an interdisciplinary scientist, dating back to high school, when he replicated a scanning tunneling microscope by himself. We discuss the tool that his lab has recently developed, a protein structure that grows over time inside single cells resulting in a cell metronome that can be coupled with colored markers responsive to cellular events to record their position over time. We discuss how Adam, his postdoc first author, and his lab took inspiration to build such a tool from the annual growth of trees. We then compare protein-based versus nucleic acid-based recorders of cellular events, and their relative limitations and promises. We discuss technical questions such as how to control not to perturb cells, time resolution, and multiplexing possibilities. Finally, we reason on the futuristic applications in vivo to monitor the molecular events of the mouse brain at the level of single cells along time for extended periods of time. So looking forward to seeing what Adam and the Cohen lab achieve in the next few years!
If you liked this episode, please consider subscribing to The Biotech Futurist on Spotify, Apple Podcast, Stitcher, Google Podcast, or your favorite platform, and leaving a positive review. The growth of this podcast depends critically on word-of-mouth. Thank you for your help. Follow The Biotech Futurist on Instagram and YouTube, and DM or email me if you have any curiosity. You can always download the transcript of this episode and find the links to the papers we mention on my website, lucafusarbassini.com. The jingle is by Gabriele Fusar Bassini.
RESOURCES
Adam’s lab at Harvard: http://cohenweb.rc.fas.harvard.edu/
[ACADEMIC] Time-tagged ticker tapes for intracellular recordings: https://www.nature.com/articles/s41587-022-01524-7
Q-State Biosciences: https://www.qstatebio.com/

Clinical Trials In Liquid Biopsy For The Diagnosis, Monitoring, And Stratification of Cancer Patients | Chiara Cremolini

What if we could detect a tumor, monitor for metastasis, and track the response to therapeutics from a simple blood draw instead of an invasive tissue biopsy?
Today I have the pleasure to discuss state-of-the-art liquid biopsy techniques with Professor Chiara Cremolini, who I met virtually during my time in Pisa. Chiara is an Associate Professor in Medical Oncology at the University of Pisa, where she performs translational research, devoted to the care of patients with malignant gastrointestinal cancers.
Chiara and I discuss the revolution brought about by the introduction of liquid biopsy in the cancers field. Liquid biopsy aims to monitor tumors from simple blood draws, to detect their response to treatments, monitor for metastasis after resection, and much more. It is currently based mostly on the analysis of circulating tumor DNA. We analyze a few applications and future possibilities of liquid biopsy for cancers, with a special focus on gastrointestinal tumors, Chiara’s area of expertise. This is also a great occasion to dissect the structure of clinical trials, and explain terms we often hear but fatigue to fully understand, such as primary end points. We put all this in the frame of Chiara’s life as a clinician, researcher, and teacher, to really immerse into what patients’ care in the cancers field looks like from the perspective of a physician, then we move on to study two recent clinical trials that greatly showcase applications of liquid biopsy. One such application is to stratify patients according to liquid biopsy-predicted response to treatments such as chemotherapy, so to spare unnecessary toxic chemotherapies if patients don’t need them, personalizing a field in which historically we could not do much more than standardizing care for very different clinical situations. The second application of liquid biopsy that we describe helps to decide when a patient can receive a second round of monoclonal antibody treatment after their resistance to such treatments has decreased enough. Looking forward to seeing what Chiara and her collaborators achieve in the next few years, but I’m pretty sure they are giving a lot for cancer patients daily, outside of scientific publications and the news!
If you liked this episode, please consider subscribing to The Biotech Futurist on Spotify, Apple Podcast, Stitcher, Google Podcast, or your favorite platform, and leaving a positive review. The growth of this podcast depends critically on word-of-mouth. Thank you for your help. Follow The Biotech Futurist on Instagram and YouTube, and DM or email me if you have any curiosity. You can always download the transcript of this episode and find the links to the papers we mention on my website, lucafusarbassini.com. The jingle is by Gabriele Fusar Bassini.
RESOURCES:
DYNAMIC clinical trial: https://gicancer.org.au/clinical-trial/dynamic-iii/
[ACADEMIC REVIEW] Circulating Tumor DNA Analysis in Colorectal Cancer: From Dream to Reality: https://ascopubs.org/doi/full/10.1200/PO.18.00397
[ACADEMIC] Circulating tumor DNA to guide rechallenge with panitumumab in metastatic colorectal cancer: the phase 2 CHRONOS trial: https://www.nature.com/articles/s41591-022-01886-0
[ACADEMIC] Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer: https://www.nejm.org/doi/full/10.1056/NEJMoa2200075
 

Trends in Aging and Rejuvenation Research | Eleanor Sheekey

What if we could treat aging as any other disease?
Today I am excited to meet Eleanor Sheekey on my podcast. Eleanor is a PhD student at the Cancer Research UK Cambridge Institute, where she focuses on p53 biology. Eleanor has a beautiful YouTube channel where she distills the most innovative research in aging with a creative and engaging rhythm, The Sheekey Science Show.
Eleanor and I go through some of the most promising trends in aging research (2022). This is not a technical episode, but rather an accessible introduction to longevity research. For most of the topics we explore, you can also find short videos on Eleanor’s YouTube channel to dig deeper and find more references to papers and reviews. Eleanor and I discuss how difficult measuring aging is, and how difficult it is to define the onset of aging, which should be known if we want to intervene on it. We define lifespan and healthspan, and consider quite a few biological mechanisms that are known to deteriorate with aging, including cellular senescence, protein aggregation and neurodegeneration, telomere shortening, accumulation of somatic mutations, changes in the gut microbiome, and more. We also describe a few innovative therapeutics being tested in cells and mice. This discussion does not aim to be exhaustive, in fact, we focus mostly on less popularized ideas, most of which are still far from the clinic, rather than better discussed molecules, on which you can still learn on Eleanor’s channel. We also discuss why the cloning of the sheep Dolly matters for aging research, and an example of vision restoration by cellular reprogramming with Yamanaka factors, one of the futuristic avenues for aging therapeutics. Eleanor clarifies the two main directions of research in the longevity space: protective strategies that try to slow down aging, and rejuvenation strategies that try to reverse it. Longevity is really an exploding field, and Eleanor’s contribution as a scientist and a youtuber will be as great!
If you liked this episode, please consider subscribing to The Biotech Futurist on Spotify, Apple Podcast, Stitcher, Google Podcast, or your favorite platform, and leaving a positive review. The growth of this podcast depends critically on word-of-mouth. Thank you for your help. Follow The Biotech Futurist on Instagram and YouTube, and DM me if you have any curiosity. You can always download the transcript of this episode and find the links to the papers we mention on my website, lucafusarbassini.com. The jingle is by Gabriele Fusar Bassini.
[OUTREACH] The Sheekey Science Show on YouTube: https://www.youtube.com/c/thesheekeyscienceshow
[ACADEMIC] Reprogramming to recover youthful epigenetic information and restore vision: https://www.nature.com/articles/s41586-020-2975-4