Sarah Teichmann, an international pioneer of single cell research

Sarah and her team develop computational methods to explore genomics and biology, and have transformed our understanding of human health and disease. She is a proponent of collaboration, open data and open science.

Here Sarah tells us about how she came to be so interested in understanding cells, and what makes her tick.

Sarah grew up in South West Germany. With an American mother and a German father, she and her two younger sisters learned both English and German and went to the multilingual European School in Karlsruhe.

Sarah was an all-rounder, she played a lot of sports including handball and tennis and was a keen skier. She also really enjoyed languages, learning French and Latin and reading simple books in other languages as a teenager. She even wrote one of these books for young teens.

Sarah explained: “My dad was an electrical engineer, and my mum lectured in German Literature, teaching teachers – so I grew up valuing learning and knowledge. When you’re learning a language it’s helpful to read a lot, but the stories and words need to be simple enough to understand. My mother asked me to co-write one of these easy-read books for 13 or 14 year olds who were learning English. I made up the story ‘Teenage Detectives’, a bit like a Famous Five story, and we wrote it together.”

Sarah studied for the European Baccalaureate, which is broader than ‘A’ levels. She covered 10 subjects, including three key subjects at depth: maths, physics and chemistry.

“My chemistry teacher, Walter Henderson, really got me into science. His teaching was inspiring and as part of that he ran an after-school science club,” said Sarah. “I did a research project on metabolism which I really enjoyed, and it got me thinking about cells and how they work. He was also very supportive of my wish to go to university in Cambridge.”

While at school, Sarah read an article in Scientific American about the discovery by researchers in Cambridge of zinc finger proteins, and how they can regulate genes. She found this fascinating and discovered she wanted to study the molecular basis of life. Luckily, Sarah’s school offered support to students wanting to go to Cambridge University, and she got a place at Trinity College to read Natural Sciences.

“It was clear that Cambridge was a very exciting place for biochemistry and molecular biology, and I loved being an undergraduate at Trinity College. I was encouraged to do a full mixture of subjects, including physics, maths and chemistry, not solely biochemistry. It stood me in really good stead, giving a wonderful foundation to build on. It also gave me a taster of programming, so I wasn’t scared of it later in my computational biology PhD. I met lots of friends there too, students from many different subjects.”

At the same time, Sarah also met her husband-to-be who was at St Johns College, next door to Trinity.

Sarah worked very hard - the science was difficult due to the broad range of subjects she’d studied at school, rather than focused science ‘A’ levels, but by the end of the year Sarah came top of Natural Sciences in Trinity College. This success led to an academic scholarship which provided some very welcome financial support from the college. This support continued as she went on to be joint top of her University year in Biochemistry final exams.

Sarah decided to do a PhD with Cyrus Chothia at the Medical Research Council Laboratory of Molecular Biology (LMB), also in Cambridge, after reading his paper on 1,000 families of proteins.

“This was the mid 1990’s and was at the beginning of bioinformatics, when many people didn’t really understand the point of it. The sequences of lots of bacterial genomes were becoming available, and I wanted to use those genomes to understand proteins, and compare them with known protein structures. We were surprised to see how long and complex these bacterial proteins were, and also how few protein families there were. We could then use the data to see how genes evolved.”

Sarah’s PhD research led to a post-doctoral position in London at UCL with Janet Thornton, moving onto studies into how biological systems could be represented as networks.

“Lots of DNA sequences had recently become available, and we could use them to reveal networks of proteins, how these proteins combined with each other. This new network theory was really exciting, and so powerful to be able to visualise the molecular interactions between proteins.”

After two years, in 2001, Sarah was recruited back to the LMB in Cambridge as a group leader, where she spent the next 12 years using network theory to look at the evolution of transcription regulatory networks - how genes are switched on and off in cells. Unusually, within her group she combined theoretical, computational work, with wet-lab work. The biochemical experiments could test the computational theories, which proved very successful. By 2013, she had published more than 70 papers with her many co-workers and collaborators, including foundational work on the assembly of protein complexes. She had also married her long-term partner and had two children.

After the birth of her second daughter, Sarah was recruited by Janet Thornton, who had moved to the Wellcome Genome Campus. Sarah took up a joint position as Research Group Leader at EMBL’s European Bioinformatics Institute (EMBL-EBI) and Senior Group Leader at the Wellcome Sanger Institute. This allowed her to continue with both computational research and the biochemical experiments on gene expression, but at a much greater scale.

“One of the exciting things about joining EBI and Sanger at this time was that single-cell genomics was really taking off, and with five colleagues, I co-founded the Sanger-EBI Single-Cell Genomics Centre. We could see which genes are expressed in individual cells, to understand gene regulation, and specifically the cells and regulatory networks of the immune system and its response to pathogens.

“Having a foot in both computational and wet-lab camps meant we could test theories experimentally, and also use bioinformatics to understand and validate the biochemical data.”

In 2016, Sarah was appointed to Head of the Cellular Genetics Programme at the Sanger Institute. This is a technology-driven programme, using cutting-edge methods to understand cells, from their identity and regulation, to how they change during development, health, disease and aging. At the same time she co-founded the international Human Cell Atlas (HCA) consortium with Aviv Regev from the Broad Institute. The Human Cell Atlas consortium aims to map every cell type in the human body, creating ‘Google maps’ of health and disease. This consortium has already mapped more than 8.5 million cells from 14 organ systems, which among other things has identified new cell states involved in asthma, revealed brain development pathways, and helped understand how the placenta forms.

I asked Sarah how she managed to juggle all her roles, from Programme Head and member of the Board of Management at the Sanger Institute, to continuing her research group and co-chairing the HCA Organising Committee. Sarah also has roles as Director of Research at the Cavendish Laboratory at the University of Cambridge (every Tuesday), and Senior Research Fellow at Churchill College. Not to mention having a family.

Sarah laughed and said: “I am very lucky to have a great team of people, it just wouldn’t be possible to do this on my own. Collaboration is key as with so many things, and we can achieve so much more together than striving alone. There is also a great synergy between these different roles, with each feeding into the others.”

Sarah has excellent support from Lizzy Langley, Sarah Aldridge and others in Cellular Genetics, and from Kerstin Meyer as her right hand woman in her research group.

“For the global HCA consortium, the partnership with Aviv who co-chairs the Organising Committee is crucial, and there are many, many other important people involved, from Sten Linnarsson and Piero Carninci, to executive staff here and at the Broad Institute. It’s taken a few years to get the team structures in place, but now we have them, and have great people supporting all of these efforts.”

Janet Thornton became Sarah’s mentor during her post-doc in London, and has continued to play an important role in her career.

“Janet has so much wisdom, she is very straight talking and supportive and I’ve benefitted hugely from her ongoing mentorship over the years. I’ve also been very lucky to have been supported by other people, such as Cyrus Chothia, Carol Robinson and now, Mike Stratton is also acting as a mentor and supporter for my career. I’m grateful for all of this inspiration. ”

Sarah now tries to pay this mentorship and support forward.

“Equality is very important to me, and I try to foster a culture that supports people, whatever their role, gender or personal circumstances. Both Cellular Genetics and the HCA have very bottom-up cultures, with projects driven by students and post-docs. We try to ensure that everyone gets support and recognition for their work.”

“We’ve also got fabulous support staff, who are integrated into the programme, and who understand the system and the science. This means that the system works, and breeds a culture of success within Cellular Genetics.”

Sarah’s daughters are now aged 7 and 12.  She and her husband share the parental responsibilities.

“I love to relax with my family, and sports are also really important to me. At Cambridge University, I played basketball and tennis. Now I really enjoy running and cycling, and try to bike to work at the Genome Campus as often as I can.” Ever efficient, Sarah adds: “My ideal is combining both family and exercise, by playing sports together.”

I asked Sarah what is inspiring her right now.

“The Human Cell Atlas is completely transforming what we know about the body, and I am fascinated how we are discovering the ‘innerverse’ – the cells within us. The HCA is creating a reference map of tissues, and this is already starting to help clinicians understand disease. There are now more than 1,600 people involved in the HCA, internationally.

“One hugely inspirational aspect is how people in the HCA are coming together in really challenging circumstances to study COVID-19, contributing our scientific expertise to combat the COVID-19 pandemic. From around the world, researchers are pooling data and resources to find out which cells are likely to be involved in transmission, and looking at the response to SARS-CoV-2. It is incredible how fast this research is moving, and I am honoured to be part of it.”