Exploring all things genetics. Dr Patrick Short, University of Cambridge alumnus and CEO of Sano Genetics, analyses the science, interviews the experts, and discusses the latest findings and breakthroughs in genetic research. To find out more about Sano Genetics and its mission to accelerate the future of precision medicine visit: www.sanogenetics.com
EP 111: Combining human and machine intelligence in protein engineering with Dr. James Field, CEO of LabGenius
Nov 09, 2023
Show notes
In this episode of The Genetics Podcast, we welcome Dr. James Field, founder and CEO of LabGenius. Join us as we delve into LabGenius' cutting-edge approach that utilises machine learning, artificial intelligence, and sophisticated robotics to advance antibody discovery and drug development. As a bonus, learn about James’ path from scientist to CEO, and how he created LabGenius. Timestamps: 00:00 Introduction 01:04 The genesis of LabGenius: protein engineering 04:06 Progressing from human intuition and rules-of-thumb to a mathematically-driven approach to protein synthesis 05:24 Redefining the relationship between human and machine 08:38 Multi-dimensional optimisation: an iterative machine learning approach to design and test various molecules 11:20 The LabGenius Process to developing antibodies: sequencing, testing mammalian expression, and functional cell-based assays 12:50 The relative scalability of functional cell-based assays 14:30 How LabGenius is tackling the bottlenecks in finding antibodies to cure cancer 15:52 Applying protein engineering beyond antibodies to enzymes and other biological molecules 18:12 The challenges in scaling clinical trials and the choice to engage with partners 19:24 James’ shift from scientist to CEO: Overcoming the challenges of fundraising and finding smart investors who share your vision 24:40 James’ entrepreneurial spirit: wanting to build something that is worth the tough journey 26:10 The biggest challenges to creating LabGenius and lessons learned from starting a company 29:00 Navigating the complexities of partnering with large pharma and biotech companies 30:42 Novel technologies on the horizon that redefine what it means to be healthy 32:48 Future Frontiers: The potential for in-silico models in advancing drug discovery 34:58 Closing Remarks
EP 110: Educating the next generation of genomics talent, and the intersection of genetics and environment in cancer with Barbara Kraatz Fortini
Oct 26, 2023
Show notes
On this episode of The Genetics Podcast we welcome Dr. Barbara Kraatz Fortini, Associate Professor of Genetics at Keck Graduate Institute (KGI). Tune in to learn about Barbara's research on non-coding variants in colorectal cancer and the interplay between genetics and the environment on lifetime cancer risk. As the Program Director for the MS in Human Genetics and Genomic Data Analytics at KGI, Barbara also shares her insights in genomics education for future scientists, physicians, researchers, and counsellors. You don’t want to miss this riveting episode! Timestamps:
0:00 Intro 0:42 A whistle-stop tour of Barbara’s career: an early emphasis on teaching, her desire to cure cancer, and her path to researching the role of genetics in colorectal cancer 04:23 The majority of risk for colorectal cancer comes from non-coding, summative variants in the genome 5:28 Interplay between the environment and genetics in lifetime risk for developing cancer 07:23 Benefits of the highly collaborative nature of genomics research 9:42 The impacts of gene expression from cells to organ systems 12:10 Mysteries in the ultraconservative and noncoding regions of the genome 13:40 Barbara’s role as an educator: how to adapt the genetics curriculum amidst continual discoveries in research and technology, and how she created the MS in Human Genetics and Genomic Data Analysis program 19:50 Promoting retention, accessibility, and innovation in the genetics classroom 22:20 Shifts in genetics education: RNA editing, gene expression, and structural variation 24:40 The incredibly resiliency of the human genome 26:08 Various career paths of Barbara’s students 28:54 Promoting physician genetic literacy 32:30 What Barbara’s students are most excited about: diagnosing rare diseases in infants and promoting diversity and equity in genetics research 35:10 Closing remarks
EP 109: From the Archives: Professor Sir Rory Collins on the Origins and Future of the UK Biobank
Oct 12, 2023
Show notes
This week, we’re re-sharing one of our favorite episodes from the early days of The Genetics Podcast - one that many newer listeners may not have heard! Tune in as Professor Sir Rory Collins, Founder and Chief Executive of the UK Biobank, talks to us about the origins and evolution of this world-changing project that has catalysed a wave of new discoveries by levelling the playing field in data access. In this inspiring conversation, Professor Sir Rory Collins describes the ‘’If you build it, they will come get it” attitude of the UK Biobank. He believes that the pioneering and collaborative nature of UK Biobank means that the biggest impacts are yet to come. The conversation finishes with details on their COVID-19 work (as of 2020), which involved members from the original 500,000 strong UK Biobank cohort, as well as family members of these participants. Summary: 00:00 Introduction to the UK Biobank and its impact 01:23 Origins and purpose of the UK Biobank 06:20 Involvement of private industry in funding data collection 08:47 Access to data by academic and commercial researchers 11:07 Opportunities for enhancing participant characterization 14:25 UK Biobank's major findings expected in the next 5-10 years 15:51 Democratizing access to UK Biobank data for global researchers 17:15 Open access approach fosters creativity and peer review 19:05 Practical value of polygenic risk scores in healthcare 22:05 Participant trust in sharing data for good science 23:46 COVID-19 study: Rapid data collection and involvement of family members 29:15 Discussion of a potential UK Biobank 2.0 31:38 Future focus on omics assays and health outcome phenotyping 33:12 Phenotyping health outcomes using advanced techniques 34:42 Closing Remarks
EP 108: Drug Development in Liver Disease: Breakthroughs, Challenges, and Insights with Dimitar Tonev
Sep 28, 2023
Show notes
In this episode of The Genetics Podcast, we're joined by Dimitar Tonev, an experienced drug development consultant specialising in Hepatology and Virology. Tune in to discuss the recent reclassification of Non-alcoholic Steatohepatitis (NASH) to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), and the complexities of identifying treatments for this condition. Dimitar sheds light on the pioneering role of non-invasive biomarkers and comments on the potential impacts of the Maestro study. Join us as we dive into the world of liver disease and drug development, touching upon the breakthroughs, challenges, and ethical considerations of clinical trials. For anyone interested in liver health innovations and the future of hepatology research, this episode is a must-listen. Timestamps: 0:00 Intro 2:01 Change in the name of Non-alcoholic Steatohepatitis (NASH) to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) 8:01 Challenges with clinical trials and drug development for liver diseases 16:10 Discussing the breakthroughs and future of hepatology research 21:30 Ethical dilemmas of placebo-controlled trials 27:46 An overview of FDA's approach and stance on biomarkers and technologies in NASH/MASLD 30:40 Insights into the anticipated Madrigal approval and its significance 35:10 Closing Remarks
EP 107: Integrating Genomics and Individualised Medicine into the Mayo Clinic Healthcare System with Dr. Konstantinos Lazaridis
Sep 14, 2023
Show notes
In this episode of The Genetics Podcast, we welcome Dr. Konstantinos Lazaridis, the Executive Director of the Center for Individualized Medicine at the Mayo Clinic. Tune in to learn about the impacts of genomics and individualised medicine on rare liver diseases and advanced cancers . Discover how the Mayo Clinic actively uses genomic testing, precision medicine, and environmental interventions to improve patient outcomes. Timestamps: 0:00 Introduction 0:32 Insights into the Center for Individualised Medicine at the Mayo Clinic, including the importance of predictive genomics, research in rare and undiagnosed diseases, and the integration of genomics into healthcare 4:40 Mayo Clinic’s Program for Rare and Undiagnosed Diseases (PRaUD): challenges faced and lessons learned 8:28 The Tapestry Study: integrating genomic data into patient care plans 11:40 The Tapestry Study: challenges in implementing healthcare interventions based on genetic findings 12:10 The Tapestry Study: The path to 100,000 whole exome sequences, including exciting findings, novel diagnoses, and future projections 13:20 The impact of the exposome (environmental exposures over the course of a lifetime) on genetic risk 16:45 Untapped data sources in exposome research 18:50 Linking the exposome to direct changes in cell physiology and metabolic pathways 21:34 Sources of exposome data - from blood draws to tissue samples 22:05 Painting a picture of the Center for Individualized Medicine in 20 years 23:30 Enhancing disease prevention, particularly for germline genetic diseases 26:38 Two scientists’ views on the humbling nature of biology 27:00 Mayo Clinic’s efforts to share its findings and precision medicine model with the world 28:10 Closing Remarks
Ep 106: The Colliding World of Rare and Common Disease Genetics with Caroline Wright, Professor of Genomic Medicine at Exeter University
Aug 31, 2023
Show notes
In this episode, Patrick welcomes Caroline Wright, a leading expert in genomic medicine and Professor of Genomic Medicine at Exeter University. Listen in as they delve into the world of rare diseases, discussing the challenges in diagnosis, uses of population cohorts and, the potential of newborn screening. Caroline shares her excitement about new technologies in genomics and emphasises the importance of data sharing. Discover the significance of genetic variants and the need for cautious interpretation. Timestamps: 00:48 - An overview of Caroline’s major projects and challenges 02:32 - Deciphering developmental disorders (DDD) 05:24 - The challenges in missense variants and in silico protein structure analysis 07:25 - Impact of missed coding regions on rare disease diagnosis 10:01 - The dual challenge of increasing sample size and searching the entire genome 11:42 - Explaining ascertainment bias 15:02 - The challenge of building phenotypic databases 16:46 - Promising cohort studies for ultra-rare diseases 18:13 - Opportunities in newborn screening 20:16 - Handling incidental findings 21:22 - Caroline’s journey into genomics 24:06 - Caroline’s take on AlphaFold and other protein folding models 25:39 - Promising technologies on the horizon 26:59 - What can the rare disease world learn from the common disease world? 29:09 - Closing remarks
EP105: Warren Huff, CEO and Chairman of Reata Pharmaceuticals, shares perspectives on provocative biology and the development of treatments for rare diseases
Aug 17, 2023
Show notes
In this episode, Patrick welcomes J. Warren Huff, CEO and Chairman of Reata Pharmaceuticals. Reata is known for innovating small-molecule therapies for severe and life-threatening diseases. Listen in as Warren walks us through their approach of partnering with Universities to find scientific discoveries that could become the next generation of therapies, and Reata’s recent success developing a groundbreaking new treatment for Friedreich’s Ataxia (FA), thanks to close collaboration with patient organizations and novel use of natural history data to accelerate their clinical development.
0:00 The beginnings of Reata
2:40 Partnering with universities for breakthroughs in research
5:30 Implications of cancer prevention research on chronic diseases
11:40 Potential concerns in medical ethics and Big Pharma when developing groundbreaking treatments
13:20 Research on NRF2 and its role in treating Friedreich’s Ataxia, a genetic mitochondrial disease that leads to motor neuron decline
18:00 What is a natural history study, and how was it used in Reata’s FA clinical development?
22:50 The potential for clinical grade wearable devices
23:35 Determining clinical endpoints in clinical trials
26:00 The FDA’s approval process for rare disease treatments
32:40 Potential for expanding newborn screening programs
36:00 The generalizability of NRF2-based research to other inflammatory diseases and diseases related to mitochondrial malfunction
39:40 What is Type 3 Diabetes?
40:30 Warren’s career start as a lawyer and his journey to biotech
43:00 Searching for provocative biology
46:20 Major targets for the HSP program
48:30 Closing remarks and lessons in resiliency
EP104: Assessing the clinical utility of Polygenic Risk Scores in cancer screening with Professor Clare Turnbull
Aug 04, 2023
Show notes
Join Patrick Short and Professor Clare Turnbull, Professor in Translational Cancer Genetics at the Institute of Cancer Research, as they discuss polygenic risk scores and their application in healthcare. Delve into the complexities of predicting disease, the challenges of screening programs, and the potential impact of integrating genomics into healthcare systems. Discover the limitations and potential of polygenic risk scores and gain valuable insights into the future of personalized medicine.
0:00 Intro
1:00 Clare’s path to becoming a clinical geneticist and her research in uncovering genetic links to cancer
3:20 How do Polygenic Risk Scores help to predict disease, particularly breast cancer?
10:00 The influence of environmental and genetic effects on breast cancer presentation
11:30 Next clinical steps after determining genetic risk for breast cancer
17:30 How effective and accurate are polygenic risk scores in predicting various types of cancer, given the potential for false positives or negatives?
25:00 The potential for integrating genetic screenings and polygenic risk scores into early cancer diagnosis
27:20 How do monogenic risk scores like BRCA 1 and 2 fit into the paradigm of cancer research?
31:30 Using both monogenic and polygenic to explain population prevalence of disease
35:00 Integration of genomics and genetic screenings into the UK healthcare system
40:30 What comes after the genetic test? What is the use in identifying risk for a disease if nothing is subsequently done to prevent it?
44:50 Clare’s upcoming work in remodeling NHS systems for evidence protocols and clinical use of genetic tests
46:50 Closing remarks
EP103: Gene Writing with Tessera Therapeutics CEO, Dr. Mike Severino
Jul 20, 2023
Show notes
In this episode, Patrick is joined by Dr. Mike Severino, CEO of Tessera Therapeutics and CEO-Partner of Flagship Pioneering. Join us as Mike walks us through Tessera’s approach to treating genetic diseases by rewriting bases, exons, or even whole genes with a novel approach called Gene Writing.
0:00 Intro
1:00 What prompted you to join Flagship Pioneering?
3:32 How is Flagship able to innovate and invent novel therapies in ways that Big Pharma companies may find difficult?
5:00 Introduction to gene writing and the role of Tessera Therapeutics
8:22 The current limitations and challenges of gene writing
10:22 Gene knockouts vs gene writing – which is more useful for genetic therapies?
12:30 Reasons why the liver the most commonly targeted organ for gene therapies
19:00 Lipid Nanoparticles and their role in gene writing
22:45 How do you guide mobile genetic elements to write genes in the intended location?
25:20 Development of gene writing technology since 2018
28:15 The implications of gene writing for diseases like PKU, Alpha-1 antitrypsin deficiency, sickle cell disease, and cancer
34:00 Next steps on the way to clinical trials
36:46 Using genomics and computational biology to guide measurable outcomes in drug discovery and development
40:15 Using gene writing to address rare developmental diseases
43:32 Closing remarks
EP102: Dr. Marco Schmidt, founder and Chief Scientific Officer of BioTx.ai, on how to use artificial intelligence and machine learning in genomics research
Jul 06, 2023
Show notes
0:00 Intro
0:45 The founding of BioTx.ai
4:35 How do algorithms for ‘causal inference’ work?
6:30 Modeling gene interactions for genetic disorders
8:35 How to predict gene interactions
10:30 What happens after identifying a potential gene variant or interaction?
14:35 How can you use machine learning to determine causal relationships between gene variants and disease?
17:30 Deconvoluting genes and traits, and their impacts on effect size
19:20 Key ingredients in determining causal relationships: data and computational power
21:10 Limitations of using machine learning to find genetic determinants of rare diseases
24:30 Predicting clinical outcomes with Biotx.ai
28:05 Machine learning enhances efficiency in the pre-clinical phase
29:40 Population genomics in Germany
32:50 Marco’s career decisions – starting a company vs. continuing in academia
35:50 The pros and cons of industry
38:10 The gaps in industry and academia
41:20 Closing remarks
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