Humans are engaged in a non-stop evolutionary struggle with infectious diseases. I seek to understand how natural selection from pathogens has shaped human genetics. My research falls into two areas:
1. Malaria and the red blood cell
The genetic mutations responsible for a variety of human blood conditions - most famously sickle cell anaemia, but also the thalassaemias - make those who carry them less likely to die from malaria. We still do not understand exactly how this malaria protection works. Sickle cell and the thalassaemias are also public health concerns in their own right.
Various populations around the world have experienced malaria for many generations, and ended up with different profiles of malaria protective blood disorder genes. I use models to simulate the possible evolutionary histories behind such profiles. These models help me to understand how genetic blood conditions interact with one another and with the malaria parasite, and make predictions about mechanisms of malaria protection.
Our immune systems protect us from pathogens. A female immune system must also be capable of tolerating a foetus during pregnancy. Immune system genes known as HLAs and KIRs are critical to fighting infection, but there is evidence that they affect pregnancy too. I use mathematical models and computational simulations to understand interactions between HLAs, KIRs and pathogens. I intend to identify the genetic signatures of pathogen and reproductive selection on HLAs and KIRs, and to use models to help predict which genetic combinations lead to different health outcomes.
I am a member of the Warwick Infectious Disease Epidemiology Research centre
I studied Biological Sciences at the University of Oxford (BA, 2006) and completed a DPhil in Zoology at the University of Oxford (2011). I was a Junior Research Fellow at Merton College, Oxford (2011-2014), a Sir Henry Wellcome Postdoctoral fellow at the University of Oxford Department of Zoology (2011-2015) and between 2015 and 2016 I was a Departmental Research Lecturer in the University of Oxford Department of Zoology.
- Spensley, Katrina J., Wikramaratna, Paul S., Penman, Bridget S., Walker, Andrew, Smith, Adrian L., Pybus, Oliver G., Jean, Létitia, Gupta, Sunetra, Lourenço, José, 2019. Reverse immunodynamics : a new method for identifying targets of protective immunity. Scientific Reports, 9
- Hockham, Carinna, Ekwattanakit, Supachai, Bhatt, Samir, Penman, Bridget S., Gupta, Sunetra, Viprakasit, Vip, Piel, Frédéric B, 2019. Estimating the burden of a-thalassaemia in Thailand using a comprehensive prevalence database for Southeast Asia. eLife, 8
- Penman, Bridget S., Gupta, Sunetra, 2018. Detecting signatures of past pathogen selection on human HLA loci : are there needles in the haystack?. Parasitology, 145 (6), pp. 731-739
- Hockham , C., Bhatt, S., Colah, R., Mukherjee, M. B., Penman, Bridget S., Gupta, S., Piel, F. B., 2018. The spatial epidemiology of sickle-cell anaemia in India. Scientific Reports, 8
- Penman, Bridget S., Gupta, S., Shanks, G. D., 2017. Rapid mortality transition of Pacific Islands in the 19th century. Epidemiology and Infection, 145 (1), pp. 1-11
- Tusco, Radu, Jacomin, Anne-Claire, Jain, Ashish, Penman, Bridget S., Bowitz Larsen, Kenneth, Johansen, Terje, Nezis, Ioannis P., 2017. Kenny mediates selective autophagic degradation of the IKK complex to control innate immune responses. Nature Communications, 8
- Penman, Bridget S., Moffett, Ashley, Chazara, Olympe, Gupta, Sunetra, Parham, Peter, 2016. Reproduction, infection and killer-cell immunoglobulin-like receptor haplotype evolution. Immunogenetics, 68 (10), pp. 755-764
- Gonçalves, Bronner P., Gupta, Sunetra, Penman, Bridget S., 2016. Sickle haemoglobin, haemoglobin C and malaria mortality feedbacks. Malaria Journal, 15 (1), pp. 1-7
- Penman, Bridget S., Gupta, Sunetra, Weatherall, David J., 2015. Epistasis and the sensitivity of phenotypic screens for beta thalassaemia. British Journal of Haematology, 169 (1), pp. 117-128
- Hockham, Carinna, Piel, Frédéric B., Gupta, Sunetra, Penman, Bridget S., 2015. Understanding the contrasting spatial haplotype patterns of malaria-protective ß-globin polymorphisms. Infection, Genetics and Evolution, 36, pp. 174-183
- Levin, Bruce R., Watkins, Eleanor R., Penman, Bridget S., Lourenço, José, Buckee, Caroline O., Maiden, Martin C. J., Gupta, Sunetra, 2015. Vaccination drives changes in metabolic and virulence profiles of Streptococcus pneumoniae. PLoS Pathogens, 11 (7)
- Penman, Bridget S., Ashby, B., Buckee, C. O., Gupta, S., 2013. Pathogen selection drives nonoverlapping associations between HLA loci. Proceedings of the National Academy of Sciences of the United States of America, 110 (48), pp. 19645-19650
- Penman, Bridget S., Gupta, Sunetra, Buckee, Caroline O., 2012. The emergence and maintenance of sickle cell hotspots in the Mediterranean. Infection, Genetics and Evolution, 12 (7), pp. 1543-1550
- Penman, Bridget S., Buckee, Caroline, Gupta, Sunetra, Nee, Sean, 2010. Genome-wide association studies in Plasmodium species. BMC Biology, 8 (1)
- Penman, Bridget S., Pybus, Oliver G., Weatherall, David J., Gupta, Sunetra, 2009. Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean. Proceedings of the National Academy of Sciences of the United States of America, 106 (50), pp. 21242-21246
- Penman, Bridget S., Gupta, Sunetra, 2008. Evolution of virulence in malaria. Journal of Biology, 7 (6)
- Buckee, C. O., Jolley, K. A., Recker, M., Penman, Bridget S., Kriz, P., Gupta, S., Maiden, M. C. J., 2008. Role of selection in the emergence of lineages and the evolution of virulence in Neisseria meningitidis. Proceedings of the National Academy of Sciences of the United States of America, 105 (39), pp. 15082-15087
- Williams, Thomas N., Mwangi, Tabitha W., Wambua, Sammy, Peto, Timothy E. A., Weatherall, David J., Gupta, Sunetra, Recker, Mario, Penman, Bridget S., Uyoga, Sophie, Macharia, Alex, Mwacharo, Jedidah K., Snow, Robert W., Marsh, Kevin., 2005. Negative epistasis between the malaria-protective effects of a+-thalassemia and the sickle cell trait. Nature Genetics, 37 (11), pp. 1253-1257