Eileen Furlong | |
---|---|
Born | Eileen E.M. Furlong |
Nationality | Irish |
Alma mater | University College Dublin (BSc, PhD) |
Awards | Member of the Academia Europaea (2016) EMBO Membership (2013) |
Scientific career | |
Fields | Enhancers Chromatin topology Embryonic development Single cell genomics Transcription factors [1] |
Institutions | European Molecular Biology Laboratory Stanford University |
Thesis | Tissue-specific regulation of gene expression by the transcription factors Ying-Yang 1 and nuclear factor 1 (1996) |
Doctoral advisor | Finian Martin [2] |
Website | furlonglab |
Eileen E. M. Furlong FRS MAE is an Irish molecular biologist working in the fields of transcription, chromatin biology, developmental biology and genomics. [3] She is known for her work in understanding how the genome is regulated, in particular to how developmental enhancers function, how they interact within three dimensional chromatin topologies and how they drive cell fate decisions during embryogenesis. [1] [4] [5] She is Head of the Department of Genome Biology at the European Molecular Biology Laboratory (EMBL). Furlong was elected a member of the European Molecular Biology Organization (EMBO) in 2013, [6] the Academia Europaea in 2016 [7] and to EMBO’s research council in 2018. [8]
Eileen Furlong obtained a Bachelor of Science degree at University College Dublin, and a PhD at the Conway institute at UCD, studying transcriptional regulation of immediate early response genes in the lab of Finian Martin. [2]
After her PhD, Furlong was a postdoctoral researcher at Stanford University, in Matthew P. Scott's lab, [9] developing genomics tools to functionally dissect developmental programmes during embryogenesis. Furlong started her independent lab at EMBL in 2002, [10] and was appointed head of department [11] in 2009. Her research integrates genomics, genetics and computational biology approaches to functionally dissect the role of non-coding cis-regulatory elements in the regulation of gene expression. [12] [13] In particular, using mesoderm specification into different muscle primordia as a model system. Her group’s research has uncovered a number of properties of enhancers [14] [15] [16] [17] and enhancer-promoter communication, including pre-formed enhancer-promoter ‘loops’ [18] [19] and the ability of many enhancer’s to function even when larger chromatin topologies are perturbed, [20] [21] [22] in addition to mechanisms that allow enhancers to withstand the effects of genetic variation, including collective transcription factor recruitment, [23] [24] genetic epistasis within enhancers [25] and promoters, [26] and extensive redundancy, [27] which together contribute to canalization in developmental patterning.[ citation needed ]
Furlong’s work was credited in the development and application of genomic approaches to understand embryonic development, [28] [29] including the development of Drosophila microarrays, [30] [31] an automatic transgenic embryo sorter, [32] [33] Chromatin immunoprecipitation (ChIP) in embryos, [34] [35] [36] tissue specific [37] [38] [39] and single cell approaches [40] - which combined with genetic manipulations provided insight into developmental programmes during embryogenesis at a genome-wide scale. [41] [42]
Furlong serves on the editorial boards of the scientific journals Developmental Cell , [43] Development , [44] Molecular Systems Biology , [45] Current Opinion in Genetics Development , [46] Current Opinion in Cell Biology , [47] [48] a European Research Council (ERC) panel member [49] [50] and an organiser of the international Conferences From Functional Genomics to Systems Biology, [51] EMBL Transcription and Chromatin [52] meeting, and a keynote speaker at national and international conferences including Intelligent Systems for Molecular Biology (ISMB). [53] [54] [55] [56] [57] [58] [59] [ excessive citations ]
Furlong was elected a member of the European Molecular Biology Organization (EMBO) in 2013, [6] and a Member of the Academia Europaea (MAE) in 2016. [7] Furlong was awarded ERC advanced investigator funding CisRegVar 2013-2018 [60] and DeCRypT 2019-2023. [61] She was elected a Fellow of the Royal Society in May 2022. [62]
A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundamental subunit of chromatin. Each nucleosome is composed of a little less than two turns of DNA wrapped around a set of eight proteins called histones, which are known as a histone octamer. Each histone octamer is composed of two copies each of the histone proteins H2A, H2B, H3, and H4.
In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of itself, such as tRNA or rRNA. Promoters are located near the transcription start sites of genes, upstream on the DNA . Promoters can be about 100–1000 base pairs long, the sequence of which is highly dependent on the gene and product of transcription, type or class of RNA polymerase recruited to the site, and species of organism.
Heterochromatin is a tightly packed form of DNA or condensed DNA, which comes in multiple varieties. These varieties lie on a continuum between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a role in the expression of genes. Because it is tightly packed, it was thought to be inaccessible to polymerases and therefore not transcribed; however, according to Volpe et al. (2002), and many other papers since, much of this DNA is in fact transcribed, but it is continuously turned over via RNA-induced transcriptional silencing (RITS). Recent studies with electron microscopy and OsO4 staining reveal that the dense packing is not due to the chromatin.
In genetics, an enhancer is a short region of DNA that can be bound by proteins (activators) to increase the likelihood that transcription of a particular gene will occur. These proteins are usually referred to as transcription factors. Enhancers are cis-acting. They can be located up to 1 Mbp away from the gene, upstream or downstream from the start site. There are hundreds of thousands of enhancers in the human genome. They are found in both prokaryotes and eukaryotes.
A regulatory sequence is a segment of a nucleic acid molecule which is capable of increasing or decreasing the expression of specific genes within an organism. Regulation of gene expression is an essential feature of all living organisms and viruses.
In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from altering the number of copies of RNA that are transcribed, to the temporal control of when the gene is transcribed. This control allows the cell or organism to respond to a variety of intra- and extracellular signals and thus mount a response. Some examples of this include producing the mRNA that encode enzymes to adapt to a change in a food source, producing the gene products involved in cell cycle specific activities, and producing the gene products responsible for cellular differentiation in multicellular eukaryotes, as studied in evolutionary developmental biology.
Fotis Constantine Kafatos was a Greek biologist. Between 2007-2010 he was the founding president of the European Research Council (ERC). He chaired the ERC Scientific Council from 2006-2010. Thereafter, he was appointed Honorary President of the ERC.
Chromosome conformation capture techniques are a set of molecular biology methods used to analyze the spatial organization of chromatin in a cell. These methods quantify the number of interactions between genomic loci that are nearby in 3-D space, but may be separated by many nucleotides in the linear genome. Such interactions may result from biological functions, such as promoter-enhancer interactions, or from random polymer looping, where undirected physical motion of chromatin causes loci to collide. Interaction frequencies may be analyzed directly, or they may be converted to distances and used to reconstruct 3-D structures.
SATB1 is a protein which in humans is encoded by the SATB1 gene. It is a dimeric/tetrameric transcription factor with multiple DNA binding domains. SATB1 specifically binds to AT-rich DNA sequences with high unwinding propensity called base unpairing regions (BURs), containing matrix attachment regions (MARs).
Epigenomics is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome. The field is analogous to genomics and proteomics, which are the study of the genome and proteome of a cell. Epigenetic modifications are reversible modifications on a cell's DNA or histones that affect gene expression without altering the DNA sequence. Epigenomic maintenance is a continuous process and plays an important role in stability of eukaryotic genomes by taking part in crucial biological mechanisms like DNA repair. Plant flavones are said to be inhibiting epigenomic marks that cause cancers. Two of the most characterized epigenetic modifications are DNA methylation and histone modification. Epigenetic modifications play an important role in gene expression and regulation, and are involved in numerous cellular processes such as in differentiation/development and tumorigenesis. The study of epigenetics on a global level has been made possible only recently through the adaptation of genomic high-throughput assays.
Dame Caroline Dean is a British plant scientist working at the John Innes Centre. She is focused on understanding the molecular controls used by plants to seasonally judge when to flower. She is specifically interested in vernalisation — the acceleration of flowering in plants by exposure to periods of prolonged cold. She has also been on the Life Sciences jury for the Infosys Prize from 2018.
Albert Erives is a developmental geneticist who studies transcriptional enhancers underlying animal development and diseases of development (cancers). Erives also proposed the pacRNA model for the dual origin of the genetic code and universal homochirality. He is known for work at the intersection of genetics, evolution, developmental biology, and gene regulation. He has worked at the California Institute of Technology, University of California, Berkeley, and Dartmouth College, and is an associate professor at the University of Iowa.
Enhancer RNAs (eRNAs) represent a class of relatively long non-coding RNA molecules transcribed from the DNA sequence of enhancer regions. They were first detected in 2010 through the use of genome-wide techniques such as RNA-seq and ChIP-seq. eRNAs can be subdivided into two main classes: 1D eRNAs and 2D eRNAs, which differ primarily in terms of their size, polyadenylation state, and transcriptional directionality. The expression of a given eRNA correlates with the activity of its corresponding enhancer in target genes. Increasing evidence suggests that eRNAs actively play a role in transcriptional regulation in cis and in trans, and while their mechanisms of action remain unclear, a few models have been proposed.
A topologically associating domain (TAD) is a self-interacting genomic region, meaning that DNA sequences within a TAD physically interact with each other more frequently than with sequences outside the TAD. The median size of a TAD in mouse cells is 880 kb, and they have similar sizes in non-mammalian species. Boundaries at both side of these domains are conserved between different mammalian cell types and even across species and are highly enriched with CCCTC-binding factor (CTCF) and cohesin. In addition, some types of genes appear near TAD boundaries more often than would be expected by chance.
H3K4me3 is an epigenetic modification to the DNA packaging protein Histone H3 that indicates tri-methylation at the 4th lysine residue of the histone H3 protein and is often involved in the regulation of gene expression. The name denotes the addition of three methyl groups (trimethylation) to the lysine 4 on the histone H3 protein.
H3K27ac is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates acetylation of the lysine residue at N-terminal position 27 of the histone H3 protein.
H3K27me3 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the tri-methylation of lysine 27 on histone H3 protein.
Alexander Stark is a biochemist and computational biologist working on the regulation of gene expression in development. He is a senior scientist at the Research Institute of Molecular Pathology (IMP) at the Vienna Biocenter and adjunct professor of the Medical University of Vienna.
Asifa Akhtar is a Pakistani biologist who has made significant contributions to the field of chromosome regulation. She is Senior Group Leader and Director of the Department of Chromatin Regulation at the Max Planck Institute of Immunobiology and Epigenetics. Akhtar was awarded EMBO membership in 2013. She became the first international and female Vice President of the Max Planck Society's Biology and Medicine Section in July 2020.
Robert E. Kingston is an American biochemist who studies the functional and regulatory role nucleosomes play in gene expression, specifically during early development. After receiving his PhD (1981) and completing post-doctoral research, Kingston became an assistant professor at Massachusetts General Hospital (1985), where he started a research laboratory focused on understanding chromatin's structure with regards to transcriptional regulation. As a Harvard graduate himself, Kingston has served his alma mater through his leadership.