THE FIRC INSTITUTE OF MOLECULAR ONCOLOGY (IFOM) AND THE MECHANOBIOLOGY INSTITUTE (MBI), NUS
On 15 May 2014 the Mechanobiology Institute (MBI) and the FIRC Institute of Oncology (IFOM), Italy, entered an agreement to establish a Joint Research Laboratory (JRL) based at the Mechanobiology Institute.
For a duration of 3 years to begin with, the IFOM-MBI Joint Research Lab (JRL) will join the league of international laboratories in world-class research organizations that IFOM has established including joint labs with A*STAR in Singapore and inSTEM (The Institute for Stem Cell Biology and Regenerative Medicine) in Bangalore, India. With co-funding from both parties, the Joint Research Lab will be embarking on a project on the “Mechanobiology of Cancer”. The Joint Research Lab will be headed by Prof. G V Shivashankar of the MBI, NUS in Singapore with his counterpart Prof. Marco Foiani, Scientific Director of IFOM.
Through the MBI-IFOM partnership, further studies into the mechanisms that control nuclear dynamics and protein synthesis will be possible. Mathematical modelling and computer simulations will help predict the effect of mechanical stress on protein synthesis while cells will continue to be grown on surfaces designed to mimic those found in the body, such as bone, muscle or cartilage. By adopting a multidisciplinary approach to its research, the Joint Research Laboratory will be well placed to assess the effect of stretching or compressive forces on regulating cancer specific signaling pathways and protein synthesis.
“The Joint Research Lab will enable a strong multidisciplinary approach to understanding the mechanobiological basis of cancer by bringing together the Mechanobiology Institute, Singapore and FIRC Institute of Molecular Oncology (IFOM) – two of the world’s leading institutes”
- Prof G.V Shivashankar, Deputy Director of the Mechanobiology institute and Head of the MBI-IFOM joint
IFOM is a research institute, funded by the Italian Foundation for Cancer Research (FIRC); a non-profit organization and one of the largest of its kind in Europe. IFOM is a world leader in Cancer Research and is keen on establishing international network by partnering with first class research organizations on scientific projects in complementary areas of the institute’s scientific mandate in “Understanding cancer. The way to cure it”. IFOM recognizes that expanding in Mechanobiological aspects of cellular/nuclear/genomic mechanisms of cancer research would be important and is keen on establishing strong links with Mechanobiology Institute and NUS.
More details about IFOM international activities and scientific vision are available here:
The Mechanobiology Institute (MBI) is a recently founded Research Center for Excellence funded by the National Research Foundation, Singapore. MBI, in a short span of five years, has become a world-class research center under an active leadership, dynamic faculty and efficient administration. MBI is based at the National University of Singapore (NUS), one of the best universities in Asia and ranks amongst the top thirty in the world.
More details about MBI are available here: http://www.mbi.nus.edu.sg
THE IFOM-NUS CHAIR PROFESSORSHIP
The IFOM-NUS Chair Professorship was created out of the partnership formed between the Mechanobiology Institute (MBI) in National University of Singapore and the FIRC Institute of Molecular Oncology (IFOM), which is supported by the Italian Foundation for Cancer Research (FIRC). The recipient of this professorship is Prof. G V Shivashankar, who is also the head of the MBI-IFOM Joint Research Lab in Singapore.
Prof. G.V.Shivashankar is currently the Deputy Director of the Mechanobiology Institute, National University of Singapore. Shivashankar’s laboratory is focused on understanding the role of cell geometry on nuclear mechanics and genome regulation in living cells using a multi-disciplinary approach. He carried out his PhD research at the Rockefeller University (1994-1999) and Postdoctoral research at NEC Research Institute, Princeton USA (1999-2000). He started his laboratory at the National Center for Biological Sciences, TIFR- Bangalore, India (2000-2009) before relocating to a tenured faculty position at the National University of Singapore in 2009. His scientific awards include; the Birla Science Prize (2006), The Swarnajayanthi Fellowship (2007) and was elected to the Indian Academy of Sciences (2010). He Edited the Methods in Cell Biology series book on “Nuclear Mechanics and Genome Regulation” (2010), Elsevier Press. More recently he Heads the Joint Research Laboratory with FIRC Institute of Molecular Oncology (IFOM), Milan, Italy and was appointed as an IFOM-NUS Chair Professor in 2014.
This is the first Chair Professorship created at MBI through support from an overseas organization towards the advancement of science. MBI is honoured to be selected as a recipient for this Chair Professorship and is proud to be seen the leading research institute with bold innovative ideas in the new field of Mechanobiology.
“ In addition to support from governments, basic science needs support and contributions from foundations and private donors for bold ideas and scientific innovations. The IFOM-NUS Chair Professorship was created through a partnership with the FIRC Institute of Molecular Oncology, an institute supported by the Italian Foundation for Cancer Research (FIRC). This is the first Chaired Professorship at MBI and we hope that additional professorships will encourage further innovations and bold experiments”
-Prof. Michael Sheetz, 2013 Lasker award winner and Director of the Mechanobiology institute, National University of Singapore.
IFOM – MBI MEMORANDUM OF UNDERSTANDING
In addition to the Joint research Lab, MBI and IFOM signed an MOU to foster further research collaborations at the inaugural joint symposium held at Milan, Italy on 15 July 2014.
Views and perspectives of the Joint Research Lab according to Professor Sheetz and Professor Foiani:
RECENT SCIENTIFIC OUTCOME
Understanding how cells pre-empt collisions between the replication machinery and regions of chromatin still bound to the nuclear membrane was the focus of a collaborative study published in Cell and led by Prof. Marco Foiani of IFOM, Italy. In this study a protein known as ATR, which senses DNA damage and protects genome integrity, was revealed to respond to mechanical stimuli originating at the nuclear envelope.
Here, ATR rapidly moved to the nuclear envelope when the nucleus was stretched by changes in osmotic pressure, or when whole cells were stretched via a patch-clamp method. Once present at this site, activation of the ATR signalling pathway was found to co-ordinate chromatin condensation and nuclear envelope breakdown, which enables detachment of condensed chromatin from the nuclear envelope. Such processes ensure chromatin condensation proceeds normally and DNA replication progresses unhindered.
While ATR's role in the prevention of DNA damage was well known, the role of mechanical forces in its regulation took the researchers by surprise. It also took them into unfamiliar territory, where a fundamental biological process was regulated by basic physics. A deeper understanding of the mechanisms involved was however attained through collaboration with Prof. G.V. Shivashankar at the Mechanobiology Institute, National University of Singapore.
Traditionally, researchers have focused on the role of biochemical pathways and genetics in understanding how cells protect the genome and repair damaged DNA. However, the findings published by Kumar et al, highlight the importance of mechanical force in the regulation of fundamental biological processes.
To fully understand how mechanical forces confer a biological response, a multidisciplinary approach to the research is required. In 2014, collaborations between IFOM and MBI were cemented through the formation of the Joint Research Laboratory and chaired professorship. This relationship will continue to promote a deeper understanding of how physical forces modulate biochemical processes, and in turn, reveal new discoveries in the etiology of cancer.
ATR is a protein found in the nucleus of a cell that generates signals to sense and protect DNA from being damaged. Collaboration between the laboratories of IFOM’s Prof. Marco Foiani and MBI’s Prof. G.
V. Shivashankar has discovered that ATR’s activity is triggered by physical forces at the nuclear membrane. Physical forces imposed on the nuclear membrane by osmotic changes, or cell stretching, activated ATR. The fact that ATR can respond to mechanical stimuli was previously unknown, and this mechanism is now keenly studied in the Joint Research Laboratory. An understanding of how physical forces can affect biochemical process (in this case, DNA replication) will lead to wider discoveries into the inner workings of all cells. In particular, how cancer cells develop, and how genetic defects lead to specific diseases.
Such studies are made possible by the opportunities provided through collaborations such as that between IFOM and MBI in the Joint research Lab. The technology and tools needed to “see” and measure this phenomenon are acquired, the varied expertise of scientists allow them to ask the right questions, and unique experimental methods applied.
Published in - Kumar A, Mazzanti M, Mistrik M et al. ATR Mediates a Checkpoint at the Nuclear Envelope in Response to Mechanical Stress. Cell, 2014; 158(3):633-646
Link to the Press release about this research: http://www.ifom.eu/en/press-area/news-pressreleases/2014.php?docuID=3346