Asifa Akhtar | |
---|---|
Born | Asifa Akhtar |
Alma mater | University College London (BSc) Imperial Cancer Research Fund (now part of The Francis Crick Institute) (PhD) |
Known for | Study of Chromatin Regulation,Basilicata-Akhtar syndrome |
Awards | EMBO membership |
Scientific career | |
Fields | Chromatin Regulation |
Institutions | Max Planck Institute of Immunology and Epigenetics |
Doctoral advisor | Richard Treisman |
Asifa Akhtar is a Pakistani biologist who has made significant contributions to the field of chromosome regulation. [1] She is Senior Group Leader and Director of the Department of Chromatin Regulation at the Max Planck Institute of Immunobiology and Epigenetics. [2] Akhtar was awarded EMBO membership in 2013. [3] She became the first international and female Vice President of the Max Planck Society's Biology and Medicine Section in July 2020. [4]
Originally from Karachi, Pakistan, Asifa Akhtar studied for a BSc in biology at University College London, moving to the Imperial Cancer Research Fund (now part of the Francis Crick Institute) to gain a PhD for studying transcriptional regulation in the lab of Richard Treisman. Akhtar's postdoctoral studies in chromatin regulation were carried out in Peter Becker’s lab Germany, at European Molecular Biology Laboratory (EMBL), Heidelberg and the Adolf Butenandt Institute, Munich. Akhtar became a group leader at EMBL in 2001, moving to the Max Planck Institute of Immunobiology and Epigenetics, Freiburg in 2009, where she heads the Akhtar lab. [5] Akhtar is an editor of the Journal of Cell Science. [6] On July 1, 2020, she was elected Vice President of the Max Planck Society's Biology and Medicine Section.
Asifa Akhtar's research focus is the study of chromatin and epigenetic mechanisms. Using Drosophila melanogaster as an experimental model, Akhtar investigates how dosage compensation acts in regulation of the X chromosome. [7] [8] Studies have also focused on how the nuclear RNA helicase, DHX9, protects the genome from deleterious effects of transposon insertion. [9] More recently Akhtar has investigated how transcription fidelity is affected by changes in the nucleosome landscape. [10]
Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in reinforcing the DNA during cell division, preventing DNA damage, and regulating gene expression and DNA replication. During mitosis and meiosis, chromatin facilitates proper segregation of the chromosomes in anaphase; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed chromatin.
In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wrapped into 30-nanometer fibers that form tightly packed chromatin. Histones prevent DNA from becoming tangled and protect it from DNA damage. In addition, histones play important roles in gene regulation and DNA replication. Without histones, unwound DNA in chromosomes would be very long. For example, each human cell has about 1.8 meters of DNA if completely stretched out; however, when wound about histones, this length is reduced to about 90 micrometers (0.09 mm) of 30 nm diameter chromatin fibers.
Euchromatin is a lightly packed form of chromatin that is enriched in genes, and is often under active transcription. Euchromatin stands in contrast to heterochromatin, which is tightly packed and less accessible for transcription. 92% of the human genome is euchromatic.
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.
An insulator is a type of cis-regulatory element known as a long-range regulatory element. Found in multicellular eukaryotes and working over distances from the promoter element of the target gene, an insulator is typically 300 bp to 2000 bp in length. Insulators contain clustered binding sites for sequence specific DNA-binding proteins and mediate intra- and inter-chromosomal interactions.
A bivalent is one pair of chromosomes in a tetrad. A tetrad is the association of a pair of homologous chromosomes physically held together by at least one DNA crossover. This physical attachment allows for alignment and segregation of the homologous chromosomes in the first meiotic division. In most organisms, each replicated chromosome elicits formation of DNA double-strand breaks during the leptotene phase. These breaks are repaired by homologous recombination, that uses the homologous chromosome as a template for repair. The search for the homologous target, helped by numerous proteins collectively referred as the synaptonemal complex, cause the two homologs to pair, between the leptotene and the pachytene phases of meiosis I.
The family of heterochromatin protein 1 (HP1) consists of highly conserved proteins, which have important functions in the cell nucleus. These functions include gene repression by heterochromatin formation, transcriptional activation, regulation of binding of cohesion complexes to centromeres, sequestration of genes to the nuclear periphery, transcriptional arrest, maintenance of heterochromatin integrity, gene repression at the single nucleosome level, gene repression by heterochromatization of euchromatin, and DNA repair. HP1 proteins are fundamental units of heterochromatin packaging that are enriched at the centromeres and telomeres of nearly all eukaryotic chromosomes with the notable exception of budding yeast, in which a yeast-specific silencing complex of SIR proteins serve a similar function. Members of the HP1 family are characterized by an N-terminal chromodomain and a C-terminal chromoshadow domain, separated by a hinge region. HP1 is also found at some euchromatic sites, where its binding can correlate with either gene repression or gene activation. HP1 was originally discovered by Tharappel C James and Sarah Elgin in 1986 as a factor in the phenomenon known as position effect variegation in Drosophila melanogaster.
The Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany is an interdisciplinary research institute that conducts basic research in modern immunobiology, developmental biology and epigenetics. It was founded in 1961 as the Max Planck Institute of Immunobiology and is one of 86 institutions of the Max Planck Society. Originally named the Max Planck Institute of Immunobiology, it was renamed to its current name in 2010 as it widened its research thrusts to the study of epigenetics.
Chromatin immunoprecipitation (ChIP) is a type of immunoprecipitation experimental technique used to investigate the interaction between proteins and DNA in the cell. It aims to determine whether specific proteins are associated with specific genomic regions, such as transcription factors on promoters or other DNA binding sites, and possibly define cistromes. ChIP also aims to determine the specific location in the genome that various histone modifications are associated with, indicating the target of the histone modifiers. ChIP is crucial for the advancements in the field of epigenomics and learning more about epigenetic phenomena.
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.
Thomas Jenuwein is a German scientist working in the fields of epigenetics, chromatin biology, gene regulation and genome function.
Elisa Izaurralde was an Uruguayan biochemist and molecular biologist. She served as Director and Scientific Member of the Department of Biochemistry at the Max Planck Institute for Developmental Biology in Tübingen from 2005 until her death in 2018. In 2008, she was awarded the Gottfried Wilhelm Leibniz Prize, shared with Elena Conti, for "fundamental new insights into intracellular RNA transport and RNA metabolism". Together with Conti, she helped characterize proteins important for exporting mRNA out of the nucleus and later in her career she helped elucidate mechanisms of mRNA silencing, translational repression, and mRNA decay.
Ana Pombo is an appointed Professor (W3) of Biology at Humboldt University and senior group leader at the Berlin Institute for Medical Systems Biology (BIMSB) at the Max Delbrück Center for Molecular Medicine (MDC) in Berlin-Buch with the focus on "Epigenetic Regulation and Chromatin Architecture". Since May 2018, Pombo is an elected member of the European Molecular Biology Organization (EMBO).
H4K20me is an epigenetic modification to the DNA packaging protein Histone H4. It is a mark that indicates the mono-methylation at the 20th lysine residue of the histone H4 protein. This mark can be di- and tri-methylated. It is critical for genome integrity including DNA damage repair, DNA replication and chromatin compaction.
H3R42me is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the mono-methylation at the 42nd arginine residue of the histone H3 protein. In epigenetics, arginine methylation of histones H3 and H4 is associated with a more accessible chromatin structure and thus higher levels of transcription. The existence of arginine demethylases that could reverse arginine methylation is controversial.
H3R17me2 is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the di-methylation at the 17th arginine residue of the histone H3 protein. In epigenetics, arginine methylation of histones H3 and H4 is associated with a more accessible chromatin structure and thus higher levels of transcription. The existence of arginine demethylases that could reverse arginine methylation is controversial.
Eileen E. M. Furlong is an Irish molecular biologist working in the fields of transcription, chromatin biology, developmental biology and genomics. 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. 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, the Academia Europaea in 2016 and to EMBO’s research council in 2018.
H3S10P is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the phosphorylation the 10th serine residue of the histone H3 protein.
H3S28P is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the phosphorylation the 28th serine residue of the histone H3 protein.
H3Y41P is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the phosphorylation the 41st tyrosine residue of the histone H3 protein.