The Genetics Podcast

Latest Episodes:

EP 151: Understanding cell ageing and its role in disease with Marco Quarta Co-founder and CEO of Rubedo Life Sciences Sep 12, 2024

Show notes

0:00 Intro to The Genetics Podcast
01:00 Welcome to Marco
02:00 The areas Marco focused on during his academic career and what motivated him to found his first company
03:18 How our understanding of ageing has changed over the past two decades and some of the current big questions in ageing biology
06:01 How to get a clearer picture of the ageing process within a tissue or cell and if new technologies like single cell genomics can aid this process
11:08 Catalyst or cause? Understanding the role of cellular senescence in disease and how it impacts treatment pathways
12:54 The challenges of building a company that addresses an area of biology which sits at the core of so many diseases and disease types
16:17 Deciding on which therapeutic modality to target when using a platform biology approach
17:57 Identifying the most effective stage at which to intervene in the senescence process and if this changes dependent upon organ system or disease area
24:33 How another company founded by Marco, Turnbio, uses a different approach by focusing on turning back the biological clock rather than understanding the ageing process and intervening
31:08 Addressing if both preventative and intervention approaches are required to comprehensively treat or cure a disease
35:39 Whether there is potential to develop core therapeutics which can have a system-wide effect and address all-cause ageing
40:12 Why ‘biohacking’ therapies can present a risk to the field of ageing biology as a whole, as well as to individuals
41:18 The developing area of science or technology Marco is most excited about and which he believes is going to have a significant impact in the coming years 43:23 Closing remarks
Find out morewww.rubedolife.com

EP 150: Cracking the biological code of aging with Martin Borch Jensen, Co-Founder and Chief Scientific Officer at Gordian Biotechnology Sep 05, 2024

Show notes

0:00 Intro to The Genetics Podcast
01:00 Welcome to Martin
01:35 How a particularly large Indian meal resulted in a book about intermittent fasting and the biology of ageing
05:10 The biological mechanisms behind intermittent fasting, and whether it’s been established to extend life expectancy in humans.
10:13 What we know (and what we don’t) about the fundamentals of biological ageing and how it influences drug development
15:28 Using trial and error to identify the mechanisms and phenotypes which can improve biological age
17:20 How Gordian Biology got its name and how it links to the challenges of biological ageing
18:52 How and why Gordian’s in vivo screening approach aims to crack the code on biological ageing
23:19 Understanding the biology and genetics which make a disease occur uniquely in older individuals
26:30 How and why Gordian works with specific animal models to generate data
28:28 Exploring if there is potential to minimise use of animal models and carry out more experiments in silico
33:31 The phenomenon of chronological age testing and improvement – and whether or not to believe the hype
39:35 How the lack of sustainable business models in the field may be limiting progress, causing companies to shift their focus to treating age-related diseases instead of tackling the ageing process itself
44:49 The role of technology, and the limitations of siloed specialties and organs-based approaches to disease
46:14 Closing remarks

EP 149: Sequencing 33 million samples to support the UK’s COVID-19 response with Tony Cox, CEO of UK Biocentre Aug 29, 2024

Show notes

0:00 Intro to The Genetics Podcast
01:00 Welcome to Tony
02:00 What Tony was expecting going into the role of CEO at UK Biocentre, and how the COVID-19 pandemic changed his plans
03:38 Receiving a phone call from the UK government in March 2020 asking the UK Biocentre to stop all of its projects and focus on sequencing COVID-19 samples
05:12 The UK Biocentre’s scale-up process, including how many samples the UK Biocentre sequenced over the course of the pandemic
09:30 The biggest changes that enable sequencing to scale from 1,000 to 100,000 samples per day
13:33 What Tony has learned about how best to implement an accelerated, unified effort to deliver for public health
16:17 The organization’s current focus on large-scale genomics projects such as Our Future Health
18:50 The challenges which need to be overcome to deliver the Our Future Health project
22:19 How UK Biocentre preserves it samples and the logistical challenges involved
24:04 The types of projects that involve the largest-scale levels of sampling and storage
28:12 Figuring out how to integrate a preventive, sample-based approach to healthcare within the parameters of cost and scale
29:27 The future proofing of sample storage techniques
31:33 The importance of consent structure and how to utilize long-term serial sampling
33:24 The upcoming technology or projects that most excite Tony
36:19 Closing remarks
Find out moreukbiocentre.comourfuturehealth.org.uk

EP 148: Advancing veteran health through the Million Veteran Program with Dr. Mike Gaziano, professor of medicine at Harvard Medical School Aug 22, 2024

Show notes

0:00 Intro
2:00 Mike’s career prior to the Million Veteran Program (MVP), how Mike got to work on MVP, and important milestones in the project's evolution
8:30 Future goals for the Million Veteran Program in expanding and diversifying the research cohort
11:00 The roles of various omics in advancing the project's development
14:30 The most meaningful outcomes of the Million Veteran Program for Mike since its launch in 2011
19:00 Scaling opportunities after the MVP celebrated enrolling its millionth participant in November 2023
25:00 How to approach securing new funding sources as the MVP expands, while maintaining the trust of veterans in safeguarding their data
27:00 Veterans’ motivation for participating in the project: A New Way to Serve
31:00 How research directly informs patient care in the MVP39:00 Closing remarks
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EP 147: From research to delivering precision medicine in the clinic with Scott Weiss, Professor of Medicine at Harvard University Aug 15, 2024

Show notes

0:00 Intro to The Genetics Podcast
01:00 Welcome to Scott
01:55 Scott’s career highlights to date, ranging from epidemiology to the genetics of asthma and chronic obstructive pulmonary disease (COPD)
04:56 How and why Scott decided to transition into genetics
06:30 The advances in our understanding of the genetics of asthma and COPD over the past 20 years
10:00 What Scott has learned about translating genomics discoveries into clinical practice and some of the biggest challenges for implementation
13:23 Tackling the reimbursement system in US healthcare and proving the value of preventive, genomics-based care
18:19 Driving down the cost of genomics initiatives such as newborn sequencing to provide high-value impact to patients
19:45 The long-term journey of taking large-scale, longitudinal multi-omic profiling from a research context into healthcare systems
24:10 Creating health-system-associated biobanks at an effective scale and what’s required to achieve that
29:42 Where Scott believes reimbursed predictive omics will first be applied
32:10 Emerging fields in research and personalized medicine that will be key areas of development and discovery in the coming years
36:53 Large-scale prospective biobanks versus a federated approach which piggybacks on existing data collection
39:45 Scott’s current research focus
42:40 What Scott likes to do in his free time outside of academia
43:41 Closing remarks

EP 146: The biology of aging with Austin Argentieri, Research Fellow at Harvard Medical School, Affiliate Member of the Broad Institute, and Research Fellow at Massachusetts General Hospital Aug 08, 2024

Show notes

0:00 Intro to The Genetics Podcast
01:00 Welcome to Austin
01:42 What is aging and how should we think about it?
03:50 Discussion of Austin’s recent breakthrough paper on aging, including the questions he set out to answer, and the outcomes of the research
06:32 How Austin’s work focuses on using large-scale population proteomics data to create accurate estimates of biological age across diverse populations
08:10 Understanding aging in people whose protein-predicted age and chronological age diverge significantly
09:40 How a single biological estimate of proteomic age is highly predictive of all major non-cancer causes of death (within a dataset)
11:46 Validating the significance of proteomic signature in populations that are genetically and geographically distinct from the cohort on which the statistical models were trained (UK Biobank)
14:48 How not all model types are equal for estimating biological age and making generalizations from biological data across diverse populations
17:38 How far fewer than 3,000 proteins are necessary to make a prediction of biological age and how a select few are particularly significant
20:04 What is it about the 20 proteins identified by Austin’s team that make them highly predictive of biological age?
23:18 Why infamous studies searching for “fountain of youth” genes have never found any definitive answers
27:24 Why conditions associated with increased age often have high heritability, even though heritability of aging is very low
29:34 Decoding proteomic signatures for age to identify risk of developing age-related conditions
32:29 Translating this research into therapeutic development
36:51 Could protein levels associated with “decelerated” aging be replicated in someone experiencing “accelerated” aging?
39:32 How Austin became involved with the biology of aging and proteomics
42:42 What Austin and his team will be working on next
44:38 Closing remarks
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Find out more:www.austinargentieri.comFind Austin on Twitter (X)

EP 145: Navigating rare disease drug development regulations with Daniel O’Connor Aug 01, 2024

Show notes

0:00 Intro to The Genetics Podcast
01:00 Welcome to Daniel
02:04 Defining rare disease in the age of personalized medicine
04:57 Key touchpoints with the Medicines and Healthcare products Regulatory Agency (MHRA) when developing a new medicine
09:27 Improvements over the course of Daniel’s career when it comes to incentivizing and making the path to developing therapeutics for rare diseases easier
12:03 The importance of orphan drug designation and what it means for treatment development
14:28 The unique challenges within clinical trial design for rare diseases, including sample size and ethical considerations such as control arms
17:22 How to quantify the scientific rigor of ultra-rare studies and small population research
18:56 The technologies which have been most impactful during the past 20 years and those which Daniel predicts will be the most impactful going forward
22:14 Rare Therapies Launchpad: Building the infrastructure and policies to ensure patients with ultra-rare mutations are connected with potentially relevant therapies
23:19 Working with the International Rare Disease Consortium and the importance of coordinating on an international level
26:30 How to enable all people living with a rare disease to receive an accurate diagnosis, care, and available therapy within one year of seeking medical attention
29:28 How a career move from working with the MHRA to The Association of the British Pharmaceutical Industry (ABPI) has impacted Daniel’s perspective
32:17 The changes the UK could make to further improve its position as one of the best places in the world to do research
35:33 Creating greater flexibility within regulatory systems to better enable use of preventive treatments
37:26 The challenges of mitigating the uncertainties of preventive treatments and benefit-risk balance over time
38:39 Considering scientific validity versus cost of therapy when developing new preventative treatments
41:17 Closing remarks
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Find out more:Find Daniel on LinkedIn

EP 144: Research Roundup with Dr. Veera: breakthroughs in developmental disorders, Parkinson's, SLE, and Alzheimer's Jul 25, 2024

Show notes

0:00 Introduction
1:40 A recurrent de novo mutation in a noncoding region of a small nucleolar RNA gene that has been identified as one of the most common causes of neurodevelopmental disorders

This pathogenic variant escaped notice for years because it was not located in a protein coding region of the genome
It now shows potential as a target for various therapeutic developments for children with developmental disorders
See the original paper here: De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders

20:30 A new gene, RAB32, linked to Parkinson’s disease through exome sequencing of families impacted by PD

Direct interactions with the LRRK2 gene through its armadillo domain, resulting in a gain of function missense mutation
How RAB32 was discovered as a significant mutation in PD research
The strong therapeutic implications of RAB32 and LRRK2
See original papers: RAB32 Ser71Arg in autosomal dominant Parkinson's disease: linkage, association, and functional analyses and Systematic rare variant analyses identify RAB32 as a susceptibility gene for familial Parkinson’s disease

35:30 Gaining insights from rare, monogenic conditions: A monogenic cause of early onset systemic lupus erythematosus (SLE)

Making discoveries by following a biological thread, a rare privilege enjoyed by few fields like immunology
See original paper here: Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus
A related paper from two years ago on SLE and the TLR7 gene: TLR7 gain-of-function genetic variation causes human lupus

49:30 Alzheimer’s disease: Old genes, new insights

Redefining research goals to make better sense of old discoveries, in addition to making new discoveries
deCODE’s previous work on the homozygosity deficit inference
APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer’s Disease
Homozygosity for R47H in TREM2 and the Risk of Alzheimer’s Disease

59:00 Closing remarks
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EP 143: Harnessing human data in drug development with Jakob Steinfeldt, Co-Founder and Chief Scientific Officer at Pheiron Jul 18, 2024

Show notes

0:00 Intro to The Genetics Podcast
01:00 Welcome to Jakob and background on Pheiron
02:14 What made Jakob decide to start Pheiron, what the company does, and how his scientific background inspired him to found a start-up
5:24 Jakob’s excitement and inspiration around the power and potential of machine learning
07:07 Cardiology and heart failure as an example of the gap between where research needs to be compared to where it is today
10:52 Why creating the GPS for identifying patients at increased risk of disease is a challenge on multiple fronts
12:42 How Pheiron’s approach and specificity is opening up the possibility of identifying highly-relevant patients and running clinical trials at greater pace
17.35 How testing potential treatments in a highly-specific population affects the design of Phase 3 clinical trials
21:19 The types of data required to build Pheiron’s GPS - from population scale insights to deep analysis within subgroups
23:48 Whether there is a shortage of healthcare systems with robust research arms looking to participate in such collaborations
27:30 Working with patients to build a collaborative commitment to data sharing
28:22 Making the decision to start Pheiron rather than continue working in medicine or research
30:38 Core learnings from building a company from the ground up
31:35 What Jakob is currently most focused on and what he hopes to achieve with Phieron in the immediate future
34:40 Closing remarks
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Find out more:www.pheiron.comFind Jakob on Twitter (X)

EP 142: From genome to bedside: How genetics is transforming modern medical practice with Dr. Andrea Gropman Jul 11, 2024

Show notes

0:00 Introduction
1:40 Andrea’s background and how she got into the field of genetics, neuroimaging, and metabolic disorders
4:00 Insights into Andrea’s clinical practice, including the diverse families and patients she serves and her approach to clinical decision-making
6:30 How genetics and genomics have changed the diagnostic journey in the last 25 years
10:00 Insurance coverage for genetic testing as a key component of preventive and diagnostic medicine
13:00 The role of genetics and genetic research in shaping medical education and enhancing various medical specialties and subspecialties
16:00 The transformative impact on clinical care by various neuroimaging technologies, such as spectroscopy, MRIs, wearable neuroimaging devices, and more
23:50 The potential of newborn screening programs, particularly for families with a history of disease and for critically ill neonates
29:00 The onset and prevalence of diseases such as Ornithine Transcarbamylase Deficiency (OTC)
34:00 Improvements in the treatment options for genetic-based diseases
38:10 Exciting advancements in Andrea’s field and her insights on the most anticipated and groundbreaking technological innovations
41:20 Closing remarks
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