Meet the Expert: Lucy van Dorp

Question 1: How did you get interested in the field of computational biology, and what drew you to human and bacterial population genetics? 

Answer: I have always been fascinated by the process of evolution. The analysis of genome sequences offers some of the best opportunities to richly characterise evolutionary processes to better understand both us and our pathogens, as well as to test long standing theories. With genomic sequencing an expanding resource, both in terms of the number of genomes available and the diversity of what we can sequence, innovative computational approaches are required to keep continually up to date with what is possible to infer from such data. The scope for creative thought and the potential to have an impact on human understanding, health and disease really drew me to the field.

Question 2: Which area of your work most excites you and why? 

Answer: An area that has excited me for some time is the technical capacity to generate genetic material from ancient and historic material. This can range from archaeological remains, such as ancient bones and teeth, to specimens in museum and pathology collections.

It is increasingly possible to obtain genomes of good quality from such material and these genomes provide a direct observation as to how the genomic makeup of organisms has changed through time. In many cases, analysis of these types of data resources have transformed our understanding of the age of divergence of major pathogen lineages, revealed adaptive changes and informed on past patterns of transmission which are often intimately linked to human behaviours and migrations.

Question 3: You did some work on the blood of Jean-Paul Marat, a French revolutionary. How did you get involved in that?

Answer: This was such a fun project to be involved in. A long-standing collaborator Professor Carles Lalueza-Fox at the Institute of Evolutionary Biology informed us that in collaboration with the Bibliothèque Nationale de France he had received permission to take a forensic swab of the blood-stained newspaper Jean-Paul Marat was allegedly holding at the time of his death, murdered by Charlotte Corday in his bathtub in 1793.

We were interested to know if it was possible to sequence the historic DNA left on this cellulose paper and if so to infer the ancestry of the individual whose blood stained the paper. We also wanted to see if we could identify potential pathogens in the blood that might diagnose the disease responsible for the debilitating skin condition which led to Jean-Paul Marat’s extended baths.

We did indeed manage to obtain historic DNA and this allowed us to identify the bloodstain as coming from a male individual of French ancestry. Identifying possible pathogens was more challenging, though we were able to rule out many of the proposed infectious diseases that had been previously suggested as responsible for Jean-Paul Marat’s condition. Our current work suggests Marat was suffering from a fungal infection leading to seborrheic dermatitis, likely with secondary bacterial infections.

Question 4: Your research interests include antimicrobial resistance, which is one of the main challenges of our time. Has this led to any interesting collaborations with people across UCL?

Answer: Yes, antimicrobial resistance or AMR poses major challenges to both human and veterinary medicine and looks set to continue to do so. Many of the bacteria which pose the biggest AMR threats readily exchange genetic material through a process called horizontal gene transfer. This is something we can track by careful analysis of DNA sequences for example during hospital outbreaks.

One advantage of working on this important topic at UCL is the breadth of expertise in microbiology and the strong links to partner hospitals. My own work has certainly been aided by these networks and supported by the activity of the UCL Microbiology Domain  and the Precision AMR initiative.

Question 5: What do you enjoy most about teaching and what has challenged you the most during the past year? 

Answer: I really enjoy the challenge of conveying complex material in an accessible way. It is particularly rewarding when students become excited by a concept and start drawing links between different material. This past year, spanning the COVID-19 pandemic, has also been my first year of lecturing. It has been difficult at times to compensate for the lack of face-to-face interactions, but I’ve been impressed at the adaptability of students during this time period. The use of an online format has also encouraged me to think carefully about how to present work and supervise computational projects. As a result, I’ve become quite adept at sharing screens and code over different online platforms.

Question 6: Your research interests cover the evolutionary history of diseases such as COVID-19. Have you seen any evidence of similar outbreaks throughout history, and have you found that the data available now pinpoints to any new evidence with regard to the evolution of this type of disease?

Answer: Yes, we’ve been working on the genomics of SARS-CoV-2 since March 2020. The pandemic has led to unprecedented sequencing efforts and COVID-19 can really be thought of as the first pandemic of the post-genomic era. Working on sequencing data generated in close to real time over the course of the COVID-19 pandemic has offered unique opportunities to study an evolving virus adapting to human infection. The density of sampling, from countries all over the world, has highlighted to me the exceedingly complex factors underlying the dynamics of viral lineages and their patterns of transmissibility.

Working on SARS-CoV-2 has also made me reflect on our understanding of other infectious disease epidemics and outbreaks through history for which genomic sampling has been very different. It has also widened my interests to coronaviruses more broadly, including those which also infect humans, as well as those which can be found in many different vertebrate hosts.

Question 7: What’s your next big research challenge?

Answer: The genomic response to the COVID-19 pandemic has been extraordinary. Over the first 18 months of the pandemic nearly two million genomes were shared by researchers and public health agencies around the world. Prior to the pandemic we were typically working on much smaller datasets, in fact I’d never previously analysed more than 4000 pathogen genomes collectively. As such this growing dataset poses some major challenges to standard methods and computational tools which were not designed with this volume of data in mind.

Beyond just SARS-CoV-2, active monitoring of pathogen genomes is very likely to become a mainstay of our response to future epidemics. The next research challenge is to develop the methods to fully utilise these expanding resources as they continue to scale. The hope is to keep pace so that we can continue to track the evolution of pathogens and provide insights which can improve human and animal health.

Further information:

• Coronavirus new variant – genomics researcher answers key questions
• Denmark to cull mink herd over coronavirus mutation fears – here’s what the science says
• A Hint About the Affliction That Kept Marat in the Bathtub
• Lucy van Dorp's webpage
• UCL Genetics Institute
• UCL Research Department of Genetics, Evolution and Environment
• Division of Biosciences
• UCL Covid-19 Research
• UCL Microbiology Research Domain
• Precision AMR initiative
• Follow Lucy on Twitter
• Follow the UCL Genetics Institute on Twitter