Project acronym ARCHAIC ADAPT
Project Admixture accelerated adaptation: signals from modern, ancient and archaic DNA.
Researcher (PI) Emilia HUERTA-SANCHEZ
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Call Details Starting Grant (StG), LS8, ERC-2018-STG
Summary With the advent of new sequencing technologies, population geneticists now have access to more data than ever before. We have access to thousands of human genomes from a diverse set of populations around the globe, and, thanks to advances in DNA extraction and library preparation, we now are beginning to have access to ancient DNA sequence data. These data have greatly improved our knowledge of human history, human adaptation to different environments and human disease. Genome-wide studies have highlighted many genes or genomic loci that may play a role in adaptive or disease related phenotypes of biological importance.
With these collections of modern and ancient sequence data we want to answer a key evolutionary question: how do human adaptations arise? We strongly believe that the state-of-the-art methodologies for uncovering signatures of adaptation are blind to potential modes of adaptation because they are lacking two critical components – more complete integration of multiple population haplotype data (including archaic, ancient and modern samples), and an account of population interactions that facilitate adaptation.
Therefore I plan to develop new methods to detect shared selective events across populations by creating novel statistical summaries, and to detect admixture-facilitated adaptation which we believe is likely a common mode of natural selection. We will apply these tools to new datasets to characterize the interplay of natural selection, archaic and modern admixture in populations in the Americas and make a comparative analysis of modern and ancient European samples to understand the origin and changing profile of adaptive archaic alleles. As a result our work will reveal evolutionary processes that have played an important role in human evolution and disease.
Summary
With the advent of new sequencing technologies, population geneticists now have access to more data than ever before. We have access to thousands of human genomes from a diverse set of populations around the globe, and, thanks to advances in DNA extraction and library preparation, we now are beginning to have access to ancient DNA sequence data. These data have greatly improved our knowledge of human history, human adaptation to different environments and human disease. Genome-wide studies have highlighted many genes or genomic loci that may play a role in adaptive or disease related phenotypes of biological importance.
With these collections of modern and ancient sequence data we want to answer a key evolutionary question: how do human adaptations arise? We strongly believe that the state-of-the-art methodologies for uncovering signatures of adaptation are blind to potential modes of adaptation because they are lacking two critical components – more complete integration of multiple population haplotype data (including archaic, ancient and modern samples), and an account of population interactions that facilitate adaptation.
Therefore I plan to develop new methods to detect shared selective events across populations by creating novel statistical summaries, and to detect admixture-facilitated adaptation which we believe is likely a common mode of natural selection. We will apply these tools to new datasets to characterize the interplay of natural selection, archaic and modern admixture in populations in the Americas and make a comparative analysis of modern and ancient European samples to understand the origin and changing profile of adaptive archaic alleles. As a result our work will reveal evolutionary processes that have played an important role in human evolution and disease.
Max ERC Funding
1 500 000 €
Duration
Start date: 2020-01-01, End date: 2024-12-31
Project acronym FIT2GO
Project A toolbox for fitness landscapes in evolution
Researcher (PI) Claudia BANK
Host Institution (HI) FUNDACAO CALOUSTE GULBENKIAN
Call Details Starting Grant (StG), LS8, ERC-2018-STG
Summary A major challenge in evolutionary biology is to quantify the processes and mechanisms by which populations adapt to new environments. In particular, the role of epistasis, which is the genetic-background dependent effect of mutations, and the constraints it imposes on adaptation, has been contentious for decades. This question can be approached using the concept of a fitness landscape: a map of genotypes or phenotypes to fitness, which dictates the dynamics and the possible paths towards increased reproductive success. This analogy has inspired a large body of theoretical work, in which various models of fitness landscapes have been proposed and analysed. Only recently, novel experimental approaches and advances in sequencing technologies have provided us with large empirical fitness landscapes at impressive resolution, which call for the evaluation of the related theory.
The aim of this proposal is to build on the theory of fitness landscapes to quantify epistasis across levels of biological organization and across environments, and to study its impact on the population genetics of adaptation and hybridization. Each work package involves classical theoretical modelling, statistical inference and method development, and data analysis and interpretation; a combination of approaches for which my research group has strong expertise. In addition, we will perform experimental evolution in Escherichia coli and influenza to test hypotheses related to the change of fitness effects across environments, and to adaptation by means of highly epistatic mutations. We will specifically apply our methods to evaluate the potential for predicting routes to drug resistance in pathogens. The long-term goal lies in the development of a modeling and inference framework that utilizes fitness landscape theory to infer the ecological history of a genome, which may ultimately allow for a prediction of its future adaptive potential.
Summary
A major challenge in evolutionary biology is to quantify the processes and mechanisms by which populations adapt to new environments. In particular, the role of epistasis, which is the genetic-background dependent effect of mutations, and the constraints it imposes on adaptation, has been contentious for decades. This question can be approached using the concept of a fitness landscape: a map of genotypes or phenotypes to fitness, which dictates the dynamics and the possible paths towards increased reproductive success. This analogy has inspired a large body of theoretical work, in which various models of fitness landscapes have been proposed and analysed. Only recently, novel experimental approaches and advances in sequencing technologies have provided us with large empirical fitness landscapes at impressive resolution, which call for the evaluation of the related theory.
The aim of this proposal is to build on the theory of fitness landscapes to quantify epistasis across levels of biological organization and across environments, and to study its impact on the population genetics of adaptation and hybridization. Each work package involves classical theoretical modelling, statistical inference and method development, and data analysis and interpretation; a combination of approaches for which my research group has strong expertise. In addition, we will perform experimental evolution in Escherichia coli and influenza to test hypotheses related to the change of fitness effects across environments, and to adaptation by means of highly epistatic mutations. We will specifically apply our methods to evaluate the potential for predicting routes to drug resistance in pathogens. The long-term goal lies in the development of a modeling and inference framework that utilizes fitness landscape theory to infer the ecological history of a genome, which may ultimately allow for a prediction of its future adaptive potential.
Max ERC Funding
1 366 250 €
Duration
Start date: 2019-03-01, End date: 2024-02-29
Project acronym LIMBo
Project Zooming the link between diet and brain health: how phenolic metabolites modulate brain inflammation
Researcher (PI) Cláudia NUNES DOS SANTOS
Host Institution (HI) UNIVERSIDADE NOVA DE LISBOA
Call Details Starting Grant (StG), LS9, ERC-2018-STG
Summary Currently a big concern of our aging society is to efficiently delay the onset of neurodegenerative diseases which are progressively rising in incidence. The paradigm that a diet rich in the phenolics, prevalent e.g. in fruits, is beneficial to brain health has reached the public. However their mechanistic actions in brain functions remain to be seen, particularly since the nature of those acting in the brain remains overlooked. I wish to address this gap by identifying candidate compounds that can support development of effective strategies to delay neurodegeneration.
Specifically, I will be analysing the potential of dietary phenolics in both prevention and treatment (i.e delay) of neuroinflammation – key process shared in neurodegenerative diseases. To break down the current indeterminate status of “cause vs effect”, my vision is to focus my research on metabolites derived from dietary phenolics that reach the brain. I will be investigating their effects in both established and unknown response pathways of microglia cells - the innate immune cells of the central nervous system, either alone or when communicating with other brain cells. Ultimately, to attain an integrated view of their effects I will establish nutrition trials in mice. LIMBo considers both pro- and anti- inflammatory processes to preliminary validate the action of any promising metabolite in prevention and/or therapeutics.
LIMBo provides valuable scientific insights for future implementation of healthy brain diets. My group is in a unique position to address LIMBo objectives due to multidisciplinary expertise in organic synthesis, metabolomics and molecular and cellular biology, together with our previous data on novel neuroactive metabolites.
LIMBo also creates far-reaching opportunities by generating knowledge that impacts our fundamental understanding on the diversity of phenolic metabolites and their specific influences in neuroinflammation and potential use as prodrugs.
Summary
Currently a big concern of our aging society is to efficiently delay the onset of neurodegenerative diseases which are progressively rising in incidence. The paradigm that a diet rich in the phenolics, prevalent e.g. in fruits, is beneficial to brain health has reached the public. However their mechanistic actions in brain functions remain to be seen, particularly since the nature of those acting in the brain remains overlooked. I wish to address this gap by identifying candidate compounds that can support development of effective strategies to delay neurodegeneration.
Specifically, I will be analysing the potential of dietary phenolics in both prevention and treatment (i.e delay) of neuroinflammation – key process shared in neurodegenerative diseases. To break down the current indeterminate status of “cause vs effect”, my vision is to focus my research on metabolites derived from dietary phenolics that reach the brain. I will be investigating their effects in both established and unknown response pathways of microglia cells - the innate immune cells of the central nervous system, either alone or when communicating with other brain cells. Ultimately, to attain an integrated view of their effects I will establish nutrition trials in mice. LIMBo considers both pro- and anti- inflammatory processes to preliminary validate the action of any promising metabolite in prevention and/or therapeutics.
LIMBo provides valuable scientific insights for future implementation of healthy brain diets. My group is in a unique position to address LIMBo objectives due to multidisciplinary expertise in organic synthesis, metabolomics and molecular and cellular biology, together with our previous data on novel neuroactive metabolites.
LIMBo also creates far-reaching opportunities by generating knowledge that impacts our fundamental understanding on the diversity of phenolic metabolites and their specific influences in neuroinflammation and potential use as prodrugs.
Max ERC Funding
1 496 022 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
