Nuno Martins

BACKGROUND

I joined the lab in March 2016, to study the genomic topology of centromeres and neocentromeres, via super-resolution microscopy, using the innovative OligoSTORM and Exchange-PAINT technologies.

I completed my degree in 2007, in Genetics and Molecular Biology in the Faculty of Sciences of the University of Lisbon, Portugal. I then went on to do a Master's degree in 2008, in the Institute of Tropical Medicine and Hygiene, in Portugal.

Due to my love of fluorescence microscopy and cell biology, I joined Lars Jansen's ‘Epilab’ group, in 2009, in the Gulbenkian Institute of Science (IGC) in Oeiras Portugal. There I worked on the cell-cycle regulation of the assembly mechanism for CENP-A, the variant histone that seems to be the epigenetic mark for centromere specification.

Afterwards I embarked on a PhD in Bill Earnshaw’s ‘Chromosome Structure’ lab in The Wellcome Trust Centre for Cell Biology (Edinburgh, Scotland). I was interested in the new epigenetic engineering manipulations that the group was performing using a Human Artificial Chromosome, and used those tools to discover the centromere’s dualistic relationship with the silencing types of chromatin that is commonly embbeded in. During that period, I actively engaged in collaborations with the Masumoto lab (Kazusa DNA Research Institute, Japan) to further dissect the transcription-related process of CENP-A assembly, and with the Fukagawa lab (National Institute of Genetics, Japan) to characterize the chromatin signature of experimentally generated neocentromeres.

PROJECTS AND GOALS

The centromere had for a long time been considered a transcriptionally inert locus, with mostly structural function, but in the last couple of decades its epigenetic nature and transcriptionally active signature have made it an object of great interest in the fields of cancer biology, chromatin dynamics and chromosome evolution.

After studying the relationship that vertebrate centromeres have with surrounding heterochromatin, I am now devoting my time to actually visualize these domains by microscopy, and verify if indeed the centromere core exhibits a different genomic folding pattern than the surrounding pericentric heterochromatin, and how this varies from cell-to-cell and across the cell cycle. Modern genomic analysis has revealed how much the compartmentalization and folding patterns across the genome have an impact on its regulation and stability, but centromeric regions remain obscure due to their highly repetitive DNA which severely hampers sequence alignment.

With the coupling of STORM and Exchange-PAINT super-resolution microscopy and FISH staining (including the single-loci OligoPAINTS pipeline), I am visualizing at 20nm resolution the nuclear arrangement and folding of centromeric and pericentromeric domains, as well as studying any structural consequences that neocentromere formation can have on local genomic folding structures (TADs, loops, etc). I will then proceed to dissect how specific chromatin structural components contribute to the folding pattern observed. To address this, I am using microscopy, automated image analysis, synthetic biology, biochemistry and genomic analysis to hopefully further our understanding of how vertebrate centromeres behave, what makes them what they are, and how they have come about in evolution.

PUBLICATIONS

3D mapping and accelerated super-resolution imaging of the human genome using in situ sequencing

Huy Q. Nguyen, Shyamtanu Chattoraj, David Castillo, Son C. Nguyen, Guy Nir, Antonios Lioutas, Elliot A. Hershberg, Nuno M. C. Martins, Paul L. Reginato, Mohammed Hannan, Brian J. Beliveau, George M. Church, Evan R. Daugharthy, Marc A. Marti-Renom & C.-ting Wu. Nat Methods 17, 822–832 (2020). https://doi.org/10.1038/s41592-020-0890-0

Walking along chromosomes with super-resolution imaging, contact maps, and integrative modeling.

Guy Nir, Irene Farabella, Cynthia Pérez Estrada, Carl G. Ebeling, Brian J. Beliveau, Hiroshi M. Sasaki, S. Dean Lee, Son C. Nguyen, Ruth B. McCole, Shyamtanu Chattoraj, Jelena Erceg, Jumana AlHaj Abed, Nuno M. C. Martins, Huy Q. Nguyen, Mohammed A. Hannan, Sheikh Russell, Neva C. Durand, Suhas S. P. Rao, Jocelyn Y. Kishi, Paula Soler-Vila, Michele Di Pierro, José N. Onuchic, Steven P. Callahan, John M. Schreiner, Jeff A. Stuckey, Peng Yin, Erez Lieberman Aiden, Marc A. Marti-Renom, C.-ting Wu. PLOS Genetics, December 26, 2018 https://doi.org/10.1371/journal.pgen.1007872

Epigenetic engineering shows that a human centromere resists silencing mediated by H3K27me3/K9me3.

Nuno M. C. Martins, Jan H. Bergmann, Nobuaki Shono, Hiroshi Kimura, Vladimir Larionov, Hiroshi Masumoto, William C. Earnshaw.

Molecular Biology of the Cell. 2016 Jan;27(1): 177-196.

CENP-C and CENP-I are key connecting factors for kinetochore and CENP-A assembly

Nobuaki Shono, Jun-ichirou Ohzeki, Koichiro Otake, Nuno M. C. Martins, J. Cell Sci. 2015 Dec;128(24): 4572-4587. doi: 10.1242/jcs.180786

Chromosome engineering allows the efficient isolation of vertebrate neocentromeres.

Wei-Hao Shang, Tetsuya Hori, Nuno M.C. Martins, Atsushi Toyoda, Sadahiko Misu, Norikazu Monma, Ichiro Hiratani, Kazuhiro Maeshima, Kazuho Ikeo, Asao Fujiyama, Hiroshi Kimura, William C. Earnshaw and Tatsuo Fukagawa.

Developmental cell 2013 Mar 25; 24 (6), 635-648. doi: 10.1016/j.devcel.2013.02.009.

HACking the centromere chromatin code: insights from human artificial chromosomes.

Jan H. Bergmann, Nuno M. C. Martins, Vladimir Larionov, Hiroshi Masumoto, William C. Earnshaw.

Chromosome Res. 2012 Jul;20(5):505-19. doi: 10.1007/s10577-012-9293-0.

Cdk activity couples epigenetic centromere inheritance to cell cycle progression.

Mariana C.C. Silva, Dani L. Bodor, Madison E. Stellfox, Nuno M.C. Martins, Helfrid Hochegger, Daniel R. Foltz, Lars E.T. Jansen.

Dev Cell. 2012 Jan 17; 22(1):52-63. doi: 10.1016/j.devcel.2011.10.014

Epigenetic engineering: histone H3K9 acetylation is compatible with kinetochore structure and function.

Jan H. Bergmann, Julia N. Jakubsche, Nuno M. Martins, Alexander Kagansky, Megumi Nakano, Hiroshi Kimura, David A. Kelly, Bryan M. Turner, Hiroshi Masumoto, Vladimir Larionov and William C. Earnshaw.

J Cell Sci. 2012 Jan 15;125(Pt 2):411-21. doi: 10.1242/jcs.090639

Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore.

an H. Bergmann, Mariluz G. Rodríguez, Nuno M.C. Martins, Hiroshi Kimura, David Kelly, Hiroshi Masumoto, Vladimir Larionov, Lars E.T. Jansen, William C. Earnshaw.

EMBO Journal 2011 Jan 19; 30: 328-340. doi: 10.1038/emboj.2010.329.