Chemical Communications Blog

Marco Di Antonio recently published his first independent research article with ChemComm. We wanted to celebrate this exciting milestone by finding out more about Marco and his research. Check out his #ChemComm1st article: A short peptide that preferentially binds c-MYC G-quadruplex DNA

What are the main areas of research in your lab and what motivated you to take this direction?

My group is interested in developing chemical and biological tools to underpin key chemical and structural changes that DNA undergoes during ageing and diseases development. I have always been fascinated by the relevance of DNA in biology, and to apply fundamental chemistry knowledge to unravel the mysteries behind DNA biology. Indeed, I have been working within this research framework pretty much during my entire career. What attracted me the most to this research topic is the idea that human genomic DNA, which is around 2 meters long, is compacted in a volume of few m2 in a cell. The 3-dimensional architecture that DNA adopts when compacting within a cell nucleus, as well as the chemical modifications that it undergoes to achieve compaction, are key to biological processes such as cell-differentiation, ageing and cancer development. Therefore, we are very interested in understanding what is the role of chemistry and chemical modifications in DNA compaction.

Although we have distinct research projects currently ongoing in my group, they are all aimed at developing chemical biology tools to unravel the fundamental mechanisms that regulate DNA structural dynamics in the context of ageing and diseases, such as cancer. We are particularly interested in non-helical structures that DNA can adopt, and we combine chemistry and biology to investigate how the formation of such non-canonical DNA structures affect human biology.

Can you set this article in a wider context?

It has been almost 70 years since the DNA double-helical structure was described for the first time. Since then, several other DNA structures have been reported. Amongst those, G-quadruplexes have emerged as a stable alternative to the double-helix due to their thermodynamic and kinetic stability. Increasing evidence supports G-quadruplex formation in the context of living cells; therefore, developing chemical tools to target these structures against the canonical DNA double helix is essential.

Several molecules that target selectively G-quadruplexes already exists, but there is a chemical need to develop new probes that can target one individual G-quadruplex over the ~700,000 that can form in the human genome. This will allow us to investigate the biology regulated by the targeted G-quadruplex structure and disentangle it from the other G-quadruplexes present in the genome. In this manuscript, we describe a short-peptide that displays preferential selectivity for the G-quadruplex structure present in the promoter region of the oncogene MYC and negligible biding towards other G-quadruplex structures. This has a double impact in the context of G-quadruplex biology: i) it provides a starting point to the design novel peptide-based probes to target specifically other G-quadruplexes besides MYC ii) it will allow biological investigation of the role(s) played by the stabilisation of MYC G-quadruplex, which is relevant in the context of cancer treatment.

What do you hope your lab can achieve in the coming year?
Publishing our first research paper has already been an incredible achievement, considering this has happened a bit more than just a year after starting my group and in the middle of a pandemic! For this, I am particularly thankful to Andrew Jamieson and his PhD student Danielle Morgan who have collaborated with us on this project and have been extremely supportive. For the coming year, it would be great to close a couple of projects that we have currently ongoing but it is a bit too early to predict this! My group started only with a PhD student (Denise Liano) and a PDRA (Aisling Minard), to whom I am very grateful for their relentless work, and we have already come a long way so keeping this trajectory for the next year would be great. We will be expanding in October with two new PhD students joining the team, so I really look forward the vibrant scientific environment that we are establishing within the group, which is helping my creativity significantly!

Describe your journey to becoming independent researcher.

The journey to become an independent academic is not an easy one, I would lie if I said the opposite. But this does not mean that is impossible, and I would encourage anyone reading this to try without even thinking about giving up a single time, if they really want to become independent researchers.

Personally, I have studied for my MSci in Chemistry in Pavia University (2007) and continued for a PhD in Padua University (2011). During my PhD, I almost exclusively worked in a synthetic chemistry laboratory, where I developed some novel G-quadruplex binding small-molecules. After getting my PhD, I was lucky enough to get a postdoctoral offer from Cambridge University to work in the group of Prof. Sir. Shankar Balasubramanian. I have been working in Shankar’s group as a Research Associate for 4 years and then as a Senior Research Associate for 3 more years. My time in Cambridge has been scientifically transformative, I have been moving from synthetic chemistry to biochemistry, cell-biology and genomics. The amount of new skills developed and the extremely intellectually challenging environment that characterises Shankar’s group have been key to develop independent thinking and to start my academic career. It has allowed me to develop a comprehensive view of nucleic acids chemistry and biology that now is at the foundation of my research group.

In December 2017, BBSRC awarded me a David Phillips Fellowship which I have used to start my group at Imperial College Chemistry. Although my research is still very much focused on the chemical biology of nucleic acids, I felt that moving to Imperial has been key to establish my research group in a new environment that is helping me to flourish as an independent scientist.

During my last 3 years of postdoc I started to apply for independent positions, and I am not afraid to share that I failed most of those applications both for fellowships and lectureships. So, my two key pieces of advice to anyone who wants to become independent researcher are: i) give yourself plenty time to make the transition, it will take at least 1 year from applying for a fellowship to get it, even if you get the first one you apply for! So, don’t wait until the end of your contract before giving it a shot; ii) Expect to fail! This is totally normal, and you shouldn’t take it personally, but rather learn from mistakes and improve your applications!

What is the best piece of advice you have ever been given?
The best piece of advice I have been given is from my former post-doc supervisor Prof Sir Shankar Balasubramanian, who always told me: “less is more”. It sounds like a very simple sentence, but as scientists we always tend to overcomplicate things and add extra experiments or extra information in our papers. Being able to disentangle key experiments from non-essential ones, as well as writing up a research paper with the least possible amount of words and jargon, is an essential skill that every scientist needs to keep working on. This is by far the best piece of advice I ever received, and I apply it every time that I design experiments with my group members, or when I write a paper!

Why did you choose to publish in ChemComm?
This is partially connected to my answer for the question above. I love publishing scientific research in the form of a communication, as it forces you to distil out essential and important information from what can be described in more details in supplementary information. Beside the format, ChemComm allows me to quickly and effectively disseminate important proof-of-concept experiments that can be transformative for the chemical community. For us, the findings of a short peptide that shows potential for selective recognition of an individual G-quadruplex were novel and essential to be disseminated quickly. Therefore, I had no hesitation to select ChemComm as a platform to present our first paper. Furthermore, I published with Chem Comm during my post-doc and I was impressed by the quick turnaround of the editors and the smooth submission portal, so it was a very easy decision for us!

Marco obtained his MSci degree in Organic Chemistry from University of Pavia in 2007 and moved to Padua University for his Ph.D in Molecular Sciences under the supervision of Prof. Manlio Palumbo and Prof. Mauro Freccero. Marco obtained his PhD in 2011 and moved to the UK to join Cambridge University. At Cambridge, he worked in the group of Prof. Sir. Shankar Balasubramanian, where he started a scientific transition from synthetic organic chemistry to molecular and cell biology. This scientific approach across boundaries is embedded in his research group that works at the interface between chemistry and biology. In December 2017 Marco was awarded a BBSRC David Phillips Fellowship, which enabled him to move to Imperial College Chemistry to start his research group.

We’re celebrating researchers who published their first independent article with ChemComm. Professor Sílvia Osuna published her first article in 2017: Computational tools for the evaluation of laboratory-engineered biocatalysts. We wanted to find out more about Sílvia and her research – Read more below.

What are the main areas of research in your lab and how has your research progressed since publishing your first article?
The main research areas in my lab are the application and development of computational tools for evaluating laboratory-engineered enzymes, with the final goal of rationally designing new enzymes. The Feature article published in Chem. Commun. in 2017 focused on providing an overview of the available computational strategies that can be used to evaluate laboratory-engineered enzymes. Since then, we have computationally evaluated a variety of enzymes mostly through extensive Molecular Dynamics simulations (monoamine oxidase, tryptophan synthase, and alcohol dehydrogenases, among others) to unveil the role exerted by distal active site mutations on the enzyme conformational landscape. Most importantly, we have also developed new computational tools for predicting active site and distal mutations for enhanced activity (Shortest Path Map tool), which we are currently applying for altering the conformational dynamics of different enzymes. The key role exerted by remote mutations on the active sites of enzymes suggests that allostery (i.e. regulation of enzyme function by distal positions) might be an intrinsic characteristic of enzymes, which we are exploiting for enzyme evolution. Therefore, our research is now more focused on applying the developed tools to rationally design new enzyme variants rather than evaluating and explaining the enhanced activities of previously reported laboratory-engineered enzymes.

What do you hope your lab can achieve in the coming year?
I hope in the coming year we can further validate our computational tools for predicting distal active site mutations. Due to the broad sequence space of enzymes, the computational prediction of such distal mutations has been proven to be extremely challenging. However, our new tools developed open the door to new protocols based on the introduction of active site and also distal mutations. This is totally unprecedented in the computational enzyme design field, and I hope in the coming year we can further demonstrate that our developed computational tools can be successfully applied for enzyme design.

Describe your journey to becoming an independent researcher.
I received a PhD in 2010 from the University of Girona (UdG) at the Institut de Química Computacional (IQC) under the supervision of Prof. Miquel Solà and Prof. Marcel Swart. I worked on the computational study of the chemical reactivity of carbon-based compounds, such as (metallo)fullerenes and carbon nanotubes. In October 2010 I moved to the group of Prof. Houk at the University of California, Los Angeles (UCLA) thanks to the IOF Marie Curie fellowship. At that time, I started to work in the computational design of enzymes of medical and pharmaceutical interest. In December 2013, I rejoined the Institute of Computational Chemistry and Catalysis (IQCC) at the University of Girona with a postdoctoral Juan de la Cierva position. I was also awarded a Career Integration Grant (CIG) project for developing a computational protocol for designing new enzymes, and also an I+D MINECO Project together with Prof. Swart. In 2015, I obtained a European Research Council – Starting grant project (ERC-StG) to apply network models for the computational design of efficient enzymes (NetMoDEzyme), and also a 5-year Ramón y Cajal position from the Spanish government. In 2018, I was promoted to the current permanent ICREA position I currently hold. My group is now funded by the ERC-StG project, an I+D MINECO project, and a Human Frontier Science Program project.

What is the best piece of advice you have ever been given?
My grandmother used to tell me a Catalan saying “De pressa i bé, mai s’avingué”, which I believe the English equivalent would be “Slow and steady wins the race”. There are of course exceptions to the saying, but I believe it is a generally good advice that also applies in scientific contexts.

Why did you choose to publish your first article in ChemComm?
I received an invitation to submit a Feature article to ChemComm a few months after being awarded the ERC-StG project. I decided this was an excellent idea as I had already done an extensive bibliographic search for writing the ERC project. Most importantly, I like ChemComm, its published Feature articles, and its broad readership. I was also really happy to see that our published Feature article was included in the most downloaded articles of 2017 in physical and environmental chemistry. When I received a second invitation to contribute with a second Feature article in 2018, I didn’t hesitate to accept the invitation.

Sílvia received her PhD in 2010 from the University of Girona (UdG) at the Institut de Química Computacional (IQC) under the supervision of Prof. Miquel Solà and Prof. Marcel Swart. In 2010, she moved to the group of Prof. Houk at the University of California, Los Angeles (UCLA). In 2012, she rejoined the Institute of Computational Chemistry and Catalysis (IQCC) at the University of Girona with a postdoctoral Juan de la Cierva position, which was followed by a Ramon y Cajal contract, and her current permanent ICREA research professor position. Sílvia’s research lies at the interface between computational chemistry and biology. Her research focuses on the study of biochemical processes mainly related to enzyme catalysis.

Read more from our ChemComm1st authors in ChemComm Milestones – First Independent Authors

We’re celebrating researchers who published their first independent article with ChemComm. Dr Han Xiao published his first article in 2018: A noncanonical amino acid-based relay system for site-specific protein labeling. We wanted to find out more about Han and his research – Read more below.

What are the main areas of research in your lab and how has your research progressed since publishing your first article?
Understanding complex biological systems and developing novel therapeutic approaches requires explorations at the interface of chemistry and biology. The focus of our research is the development of various chemical tools that allow us to precisely probe and manipulate biological systems. We are interested in (1) adding new building blocks with novel chemical, biological, and physical properties into different biological systems; (2) enhancing the performance of chemical biological tools for a variety of applications; (3) using these tools to better understand and ultimately control various biological processes; and (4) exploring the therapeutic utilities of these tools in the context of cancer, autoimmune, and metabolic diseases. My program has a strong translational focus, seeking to initiate new clinical opportunities, and contribute to advances in chemical biology, glycobiology, and cancer immunology.
Our article demonstrates the first application of autonomous cells with the endogenous ability to biosynthesize different noncanonical amino acids and incorporate them into proteins. Noncanonical amino acid, p-amino-phenylalanine, was biosynthesized in E. coli, followed by site-specific incorporation into a specific protein residue. The resulting protein was ready for functionalization using an oxidative conjugation reaction. We are continuing cells utilizing a 21st amino acid and further examine their utility in protein evolution and therapy development.

What do you hope your lab can achieve in the coming year?
Although I have been building my independent research profile at Rice, I am actively exploring new research directions by collaborating with researchers in different fields. I hope we can tell you more of these exciting works in the coming year.

Describe your journey to becoming independent researcher.
My academic training and research experience have provided me with a broad background in multiple disciplines, which is critical for me to build up my independent research program. As an undergraduate, I supported Dr. Liu-Zhu Gong’s group (USTC) by developing flexible routes to synthesize chiral amines in alkaloid nature products. As a graduate student, I joined Dr. Peter G. Schultz’s lab at the Scripps Research Institute (TSRI). My graduate work was mainly focused on expanding the technique of genetically incorporating noncanonical amino acids in both prokaryotic and eukaryotic organisms and applying this technique for better cancer therapeutics. To further my goal of becoming a professional scientist, I started my post-doctoral research career in Prof. Carolyn R. Bertozzi’s laboratory at Stanford University, whose lab has extensive experience in studying cancer-associated glycosylation. I learned a lot from my previous advisors about how to carry out projects as well as run a lab. The different training experiences from these labs laid the foundation for the interdisciplinary program I would like to build up at Rice University.

What is the best piece of advice you have ever been given?
The best advice was given to me by my parents: Prepare for the Future.

Why did you choose to publish your first article in ChemComm?
ChemComm is a renowned journal with a large readership from all chemistry disciplines as well as interdisciplinary fields. I am very happy to publish our first work in ChemComm.

Biography Han Xiao is an Assistant Professor of Chemistry and Biosciences at Rice University. Han obtained his undergraduate degree from the University of Science and Technology of China (USTC) where he graduated with a B.S. in chemistry and an honors degree in physical science. He conducted undergraduate research in Prof. Liu-Zhu Gong’s group, focusing on organic methodology and synthesis of natural products. After graduating from USTC in 2010, Han joined the Ph.D. program at the Scripps Research Institute (TSRI). His thesis work with Prof. Peter G. Schultz focused on expanding the technique of genetically incorporating unnatural amino acids in both prokaryotic and eukaryotic organisms and applying this technique for better cancer therapeutics. In 2015, Han joined the laboratory of Prof. Carolyn R. Bertozzi as a Good Ventures Postdoctoral Fellow of the Life Science Research Foundation at Stanford University. In his postdoctoral work, he was engaged in the development of novel cancer immune therapy targeting the cell-surface glycans axis of immune modulation. In July 2017, Han started his independent research at Rice University. Find him on Twitter: @Han_Xiao2016

Hiroshi Yamagishi recently published his first independent research article with ChemComm. We wanted to celebrate this exciting milestone by finding out more about Hiroshi and his research. Check out his #ChemComm1st article: Facile light-initiated radical generation from 4-substituted pyridine under ambient conditions

We asked Hiroshi a few questions about his experience in the lab and working with ChemComm. Read more below.

What are the main areas of research in your lab and what motivated you to take this direction?

After receiving the PhD for the synthesis and fundamental structural investigation of supramolecular porous fibers and crystals, I was motivated to expand this research topic in regard to their functionality. Our group in University of Tsukuba is now focusing on the synthesis of molecular porous aggregates and investigating their host–guest chemistry and optical functions.

Can you set this article in a wider context?
The host porous crystal, Pyopen, is an attracting and counterintuitive compound. Although the constituent organic molecules are bound together via labile van der Waals-like forces (C–H···N bonds), the porous framework exhibits high thermal stability. Distinct from the conventional MOFs, COFs, or HOFs, the stability of Pyopen is based on the packing mode or the interdigitation of the molecules. We expect that the difference in the bonding regime should result in novel outcomes, and we are now investigating a series of chemical and physical characters of such molecular porous crystals sustained by van der Waals crystals. This article highlights one of the intriguing optical and chemical features of the van der Waals crystals.

What do you hope your lab can achieve in the coming year?

One of the fundamental yet challenging topics in the field of van der Waals porous crystal is to establish a molecular design strategy. Distinct from the MOFs, COFs, or HOFs, the prediction or designing of van der Waals porous crystal is yet to be established due to the extremely low bonding energy and the low directionality of van der Waals force. This topic is what I am now trying to overcome in the coming year.

Describe your journey to becoming independent researcher.

In the course of the PhD, I fortunately received an offer as a researcher from a chemical company and was really willing to join after I got the PhD. However, when I visited the UK as a guest researcher for half a year before joining the company, I occasionally met with a colleague in the University of Tsukuba there, who also visited UK for Sabbatical and proposed to me a position in University of Tsukuba. Through this experience, I understood from the heart the meaning of the sentence: “Nobody knows the future”.

What is the best piece of advice you have ever been given?

An advice from a colleague of mine was indeed impressive and encouraging to me. In the course of a discussion about a research result, he said “I hate the word ‘failure’. You did not fail, but revealed a novel fact that the reaction proceeded in a different way from what you expected”.

Why did you choose to publish in ChemComm?

ChemComm is a renowned journal that covers the diverse chemical sciences. Chemical Science is also attractive to me, but I prefer the communication format for publishing our results with urgency. Therefore, I chose ChemComm.

I am an Assistant Professor in Department of Materials Science, University of Tsukuba since 2018. I was educated at the University of Tokyo, gaining a PhD in 2018 for the development of intricate nanoporous organic and metal¬–organic architectures with distinct structural flexibility. I am currently focusing on optical resonators based on supramolecular aggregates with a view to realizing flexible lasers, displays, optical circuits and sensors. Compounds of interest covers organic linear and dendritic polymers, organic and metal–organic crystals, and organic liquid.