Well, the future seems to be close.

Ray Stevens and the Bridge Institute at USC launched a program that brings together scientists (computational biologists, structural biologists, pharmacologists), engineers, and cinematic artists in an effort to visualize an entire human cell. Leveraging the expertise of students and professions across these domains, they are working to gain a more holistic understanding of health and disease at a cellular level.

Kyle McClary, a USC Dornsife and Bridge Chemistry PhD student in the laboratory of Ray Stevens is helping to lead this initiative. He’s part of the inaugural ‘Convergent Biosciences’ class that is tackling this challenge: to create the first model of a visual cell. “This course was actually inspired by a design course,” he explains. “In cinema and arts schools, they have interdisciplinary practica where students of many disciplines come together to work on a project, sharing their unique skills to get the best possible results.”

The team of students and faculty chose the pancreatic beta cell as their their first target to model. They chose the beta cell not only because it's function is critical to human health as the body's sole source of insulin, but also because it has been extensively experimentally characterized, mathematically modelled and simulated –all data that can be leveraged. Even with a plethora of data it is a tremendously complex task. They need to collect and validate data, at first focusing on transcriptomics and proteomics data. At the same time, they are piecing together this data across many different sources and scales, connecting omics to electron tomography data taken of these cells.

McClary explains they chose the pancreatic beta cell because they wanted to “work on a system that would have benefits to human health and disease. We want to see, for example, how a drug interaction at the molecular scale impacts cellular scale physiology. This is step toward ultimately developing better diabetes treatments."

This incredible project also involves the World Building Media Lab at USC School of Cinematic Arts (well known for their Leviathon project). As a key partner in this venue, they are breaking ground in bringing visualization, immersion, and interactivity into the full cell model for use in narratives, storytelling, and ultimately, research. McClary says, “Visualization is the glue that holds our mutual understanding across scientific disciplines”. By disseminating and assembling data from a visual and immersive perspective, it provides a vehicle into a largely unfamiliar space.

We’ll be engaging and looking forward with anticipation as the team takes big strides towards solving major challenges in health and disease in the coming months.

Convergent Biosciences class lead by Dr. Ray Stevens

by Daniela Quaglia, PhD

Paul Jaschke is a newly appointed Assistant Professor at Macquarie University in synthetic biology. Before landing in Australia, Paul studied and worked for years in North America. His story? Well, it hits close to home for Autodesk Research.

Autodesk has a program called Artists in Residence thanks to which they allow artists from around the world to come and work at their facilities with state of the art equipment to imagine, design, and make anything. Based on this program, Paul was accepted at Autodesk as the first Scientist in Residence where had the opportunity to work within the Autodesk Life Sciences team, in particular on the development of two tools: the Wet Lab Accelerator and the Genetic Constructor.

‘Andrew Hessel and I had been talking for years and we had done a bit of collaboration when I was still at Stanford. Andrew asked to see how I designed viruses and I basically was using a glorified text editor, ApE (one of the most barebones Genbank file readers you can get) and a notepad. They asked me: can’t we do something better than this?’

This really excited Paul as he saw huge opportunities for a functional piece of software that could allow genetic designers to build their constructs more easily. ‘Many genetic designs start with someone sketching on a white board, and this is sort of how they modelled the Genetic Constructor tool.’ The Genetic Constructor is an extensible, open source, cloud CAD tool to drive biological design and complex DNA construction.

geneticconstructor.bionano.autodesk.com

Paul is still in contact with Autodesk and this relationship is very useful in his current independent position: ‘Once in a while, they show me their latest version, and I test it out in my lab. It's going to be a very useful piece of software, and I am very looking forward to it.’

But who is Paul and how did he get to Australia? I don’t think we can go wrong by defining Paul as a synthetic biology enthusiast. He says: ‘I heard about synthetic biology for the first time at UBC [During his PhD], and I started getting very excited about it. [Together with other scholars] I helped found the first UBC iGem team which ended up winning a golden medal at the iGEM Jamboree!'

The full immersion in the synthetic biology culture of the Bay Area during his postdoc in Prof. Drew Andy’s lab was also key for Paul's development: ‘I got to be part of the Synberc organisation: every six months all these amazing synthetic biology labs come together in a sort of private conference and share their work, and it was a very interesting jump into a deep-end education on synthetic biology.'

On his recent appointment at Macquarie University he says: ‘they were looking for someone who could complement the synthetic biology projects that were already there: namely, the Yeast 2.0 project. They wanted somebody with experience in genome design and things that would complement what the yeast people were working on but not overlap because it is a smaller university. The job description was a very good fit, and thanks to my experience in Australia [where he had travelled and worked in the past during a sabbatical year] I had identified the place as somewhere where I wanted to live.’

Starting a Lab: challenges and opportunities

Paul has agreed to give us his perspective on what starting a new lab means, together with some useful advice.

'With every starting lab there is a lag phase: mine was mainly that the laboratory was physically not ready when I got to Australia.’ When Paul arrived to Macquarie University his laboratory was not yet completed, but organization is key in academic jobs, and Paul had already planned how to keep himself busy: ‘I had grants to write, classes to organize and papers to write. I started in November 2015 and the lab was ready in March 2016. In the meantime, I was given lab space in someone else's lab.’

Paul has no doubt: ‘The main difficulty [in starting a new lab] is getting grants and finding money to do good research. I guess I've seen some funding opportunities slipping through my fingers. I would say: make that a real central aspect to your work. Rearrange your calendar around potential funding opportunities. Planning ahead is crucial. Publish, publish, publish because the grant applications are ranking you for your publication record.'

Aside from securing funding, another difficult task for a new PI is to recruit good people to work with. ‘In Australia the system is changing as Masters degree similar to the ones that are in most [of the Anglo-Saxon] world have just been introduced and there has been a phase in which it was a little more difficult to find people wanting to enroll in this new lab-based Masters degrees, but now it's getting easier,’ explains Paul. To get more and more students interested in synthetic biology Paul teaches a Masters-level class to the first year students, which is all about synthetic biology. ‘A few students already came banging at the door. This is working very well in recruiting students within our University.’

An unexpected challenge that Paul encountered is linked to the difference between the North American and the Australian administration systems. In Australia there are more stringent administrative restrictions to genetic engineering ‘so to do things that you would not think as extreme genetic engineering in the US or Canada you have to fill out of paperwork and do in separate lab space,’ says Paul. [In Australia] a list exists in which organisms are classified both on their biosafety but also based on their genetic modifications. If the organisms you are planning to use is not on the list, it automatically gets classified as Level 2, even if it is not very dangerous to work with. ‘This kind of limits your creativity because it restricts the organisms or modifications you can do compared to what you could do in other countries.’

Paul’s experience is a great example for young researchers that are in the process of applying for academic positions or setting up their new laboratory. While there are challenges to overcome, the excitement of Paul when he speaks about his research and his plans for the future is contagious. Setting up your research group is no easy task, but the passion for science and mentoring of young students are certainly making of Paul’s journey a great and positive adventure.
Dr. Daniela Quaglia is a Scientist and Freelance writer currently working as a postdoctoral researcher at Universitè de Montréal.

by Charlotte Evans, MaRS Discovery District

Last month, MaRS hosted an event with Eli Groban, a senior manager at Autodesk’s BioNano group. The focus of his discussion was cloud-based software for biological design. Eli has worked for a number of biotech companies, but he quickly realized that the tools he created were shielded by IP, meaning they weren’t shared outside of specific organizations. He wanted to evolve this system, so he started talking to Autodesk.

In the past, Autodesk projects focused on the non-living world, for example the expansion of the Panama Canal. Large, complicated projects formed its foundation, but the company is now moving into the living world. Biology is the next design revolution – and Autodesk wants to harness this idea to make a global impact.

“Autodesk scientists are going out into the community and leveraging knowledge about process to find gaps. Then they design the software to fill the gaps.”

Here’s a roundup of some of the tools Eli introduced us to at MaRS Discovery District.

Genetic Constructor - Treating Malaria in Africa

This tool has been designed for synthetic biologists/metabolic engineers, who design microbes to produce useful materials. Watch this video to learn more. So far, the Genetic Constructor leverages technology that has been used by Amyris – a company making a positive impact on the world through science– to reproduce an antimalarial treatment (artemisinin) normally taken from the Artemisia annua (sweet wormwood) plant. Artemisinin is considered one of the best therapies for malaria, but half of the people in Africa, where the disease is most prevalent, can’t afford it. This breakthrough technology has reduced the cost, increasing access to essential medical care.

Eli commented: “The Genetic Constructor enables access to a number of tools in one canvas to solve real-life problems.”

Molecule Viewer – Revolutionizing Molecular Visualization for Modern Scientists and Learners

The Molecule Viewer is an online tool that allows scientists to view and communicate 3D protein structural data. It has a strong emphasis on user experience for scientists, who can customize, explore and share 3D molecular content to use in research, education, presentation, or outreach.

Some of the features of this viewer include: creating interactive 3D molecular walkthroughs (with customized and annotated structures), sharing this authored content by generating hyperlinks (scientists can send 3D content to colleagues through a URL), compatibility with mobile/touch devices, and even smartphone virtual reality (immerse into the molecular world).


In fact, the first ever structural biology lecture conducted in virtual reality used the Molecule Viewer, and took place in Potsdam. Attendees at the EMBO ICRP Conference used cardboard VR devices to immerse themselves in the virtual molecular world through their smartphones. They were able to see how a protein structure in the eye responds to light. Try it out here.

Molecular Design Toolkit – Modelling HIV Treatments

Eli outlined the many barriers to molecular modelling, including:

• Incompatible Command Line Interface (CLI) tools 
• Limited, restrictive Graphical User Interfaces (GUI) tools 
• Managing long-running processes 
• Visualization and analysis 

He then showed us a Molecular Simulation Tools workflow for computational design and development of a molecule that could treat HIV, which moved from a 2D schematic to a 3D model, then a working model and a simulation. Autodesk BioNano has compiled and installed open source tools in cloud workflows to enable scientists to easily access a dozen computational modeling programs from a webpage.


“We’ve lowered the barriers to molecular modelling by leveraging open source software. We want specialists to build applications using these tools, which involves taking computational work and putting it in the hands of biologists.
Autodesk is constantly looking at automation and workflow, in order to make tools general enough so that lots of people can use them, but also customizable to individual use. For educational purposes all of the software is free, however the company will eventually be charging industry partners to adopt its tools.

Charlotte Evans is a senior marketing associate at MaRS Discovery District – the world’s largest urban innovation hub.

If you conduct a google image search for "plasmid map" 99% of the results will show a circular map. And that is also what I would expect - but why is that so? Throughout my scientific career I have been trained to expect the virtual expectation to match the nanoscale - plasmids are circular structures of DNA - so we depict them as such. But is that the best way?

To me this seems inaccurate and inefficient to me in many ways by now.

• First, if I could actually look at my plasmid it would likely be coiled up like a telephone cord, and nowhere near this perfect circle. 
• Second, drawing a circle takes up a bunch of real estate on paper or the screen - worst of all 90% is usually "backbone" so parts you take for granted and care about only to select the right anti-biotic resistance marker. 
• So that leads to point number three - we have zoom in every time we want to get to the important part of the map - the insert. Why is that so? Wouldn't I want to see the most important part of construct in the overview?

We abstract away in all other aspects of visualization - zoom in of an organelle vs the entire cell, data trends vs tables, etc. Why not do the same for plasmids?
So what do you think - is the circular image easier to look at and understand, or the linear one?

Linear, condensed view of pET26b with inserts

Linear, extended view of pET26b with inserts

Traditional plasmid view of pET26b

Comment on the post or on our social media channels to let us know what you think!

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