Lab on a Chip Blog

We are delighted to introduce our latest Lab on a Chip Emerging Investigators, Jonathan Song and Shaurya Prakash!

Jonathan Song is an Assistant Professor of Mechanical and Aerospace Engineering and Faculty Member of the Comprehensive Cancer Center at the Ohio State University (OSU).  He received his B.S. in Biomedical Engineering (BME) from Northwestern University and his Ph.D. in BME from the University of Michigan while working in the laboratory of Dr. Shu Takayama.  He completed a post-doctoral fellowship in the laboratory of Dr. Lance Munn in the Edwin L. Steele Laboratory at Massachusetts General Hospital and Harvard Medical School.  Since 2014, he has been a faculty member at OSU where he leads an interdisciplinary lab that applies microtechnology, principles from tissue engineering, and quantitative engineering analysis for studying the physical dynamics of tumor and vascular biology.  As a faculty member, he has received the NSF CAREER Award, the American Heart Association (AHA) Scientist Development Grant, and the OSU Comprehensive Cancer Center Pelotonia Junior Investigator Award.  His research has been funded by the National Institutes of Health (NIH), NSF, AHA, American Cancer Society (ACS), and the OSU Institute for Materials Research.

Shaurya Prakash is an Associate Professor of Mechanical & Aerospace Engineering and Infectious Diseases Institute (IDI) Thematic Program Director (for Prevention, Detection, and Therapies) at The Ohio State University (OSU). He graduated with a Ph.D. in Mechanical Engineering from the University of Illinois at Urbana-Champaign in 2007 and with a B.S. also in Mechanical Engineering from the University of Arkansas, Fayetteville in 2001. He has been on the faculty at The Ohio State University since fall 2009 where he directs the Microsystems and Nanosystems Laboratory. His research group focuses on designing, fabrication, and characterization of microsystems and nanosystems for applications in healthcare and engineering biology, water purification, and alternate and renewable energy. The main goals of their research are to: provide a scientific and technological solution to the pressing problems of a rapidly evolving modern society, and educate ourselves, our students, and the community we serve.

Read their Emerging Investigators Series article “Flow dynamics control endothelial permeability in a microfluidic vessel bifurcation model” and find out more about them in the interview below:

Your recent Emerging Investigator Series paper focuses on the role flow dynamics play in endothelial permeability in a microfluidic vessel bifurcation model. How has your research evolved from your first article to this most recent article?

Jonathan: This is a very nice question.  I have been thinking of flow dynamics and generally blood vessel remodeling and angiogenesis for quite a long time now and how microfluidics is a very powerful approach for probing this biology.  This interest had first crested during my post-doc where I published a paper in 2011 with my post-doc advisor Dr. Lance Munn in PNAS (https://doi.org/10.1073/pnas.1105316108), which was also highlighted very nicely by Lab on a Chip when this article was first published (DOI: 10.1039/c1lc90131a).  Through this work, I began to fully understand and appreciate how endothelial cells that line intact blood vessels have the capacity to integrate multiple extrinsic signals, both fluid mechanical and biochemical, to determine their angiogenesis fate.

This most recent article is a bit different and I consider a significant technical advancement because of the bifurcating vessel geometry produced by microfluidic system design.  Previous microsystems that I and others had primarily used were mostly straight or parallel channels that do not reconstitute how actual blood vessels branch into two daughter vessels.  My graduate student Ehsan Akbari came up with a clever design that we described in this latest article and enabled the results that we reported.

Shaurya: Over time, my research has evolved in many ways. My first few research articles on microscale reacting gas flows (microcombustion) in millimetre scale channels really started to establish many of the fundamental insights to reacting flows in a new type of configuration. Since then, observing the trends in my work, I see that my research has dealt with developing devices for understanding microfluidic and nanofluidic flows in a variety of configurations spanning a large range of applications from healthcare to energy and water. The goal has always been to develop science to enable new technology for solving problems important to modern society. This particular article on endothelial permeability follows (at least in my mind!) the natural extension of developing novel microfluidic systems and probing fundamental transport characteristics, which in this case happens to be for an important element in biology.

What aspect of your work are you most excited about at the moment?

Jonathan: Because of my training in microfluidics, I think I will always be excited about developing new systems and applying them to study a specific physiology.  However, at present I am particularly excited in studying the subcellular biophysics that orchestrate changes in endothelial remodeling and angiogenesis.  My lab is part of team along with my co-author on this article (Dr. Shaurya Prakash) and our Ohio State University (OSU) colleague Dr. Carlos Castro that was recently awarded an NIH R01 grant to specifically study this biology.  One of the experimental test beds for these studies is the microfluidic system that was first described in this article.

Shaurya: Our microfluidic platform provides us tremendous flexibility in evaluating bio-chemical-electrical-mechanical aspects of the endothelium. In particular, the ability to systematically evaluate effects of a variety of mechanical, electrical, and chemical stimuli to elicit biological responses from endothelial cells present an exciting avenue for future research that can probably help us to think about how we can truly begin to reach in the domain of ‘engineering biology’.

In your opinion, what is the biggest insight into the mechanisms that control vessel function presented by your research?

Jonathan: I believe it is that the impinging stagnation point flow at the base of our bifurcating microfluidic model (which we term in the article as bifurcated fluid flow or BFF) imparts a vessel stabilizing effect that is nitric oxide (NO) dependent.  This outcome has prompted multiple questions that we wish to pursue in the future that relate to vessel function and vessel maturation.

Shaurya: In this paper, the evaluation of time-dependent changes to endothelial permeability under a variety of systematically controlled local flow conditions (stagnation pressure at bifurcation point, local shear stress, and transvascular flow) showed that the mechanical forces acting on the endothelial cells biochemically-mediate endothelial remodeling processes. Here we reported the first observation of the time-dependent effect of stagnation pressure at the bifurcation point on the permeability thereby introducing stagnation flows at the base of vessel bifurcations as an important regulator of vessel permeability and suggest a mechanism by which local flow dynamics control vascular function in vivo through this in vitro study.

What do you find most challenging about your research?

Jonathan: I do like pretty much all aspects of my lab’s research and appreciate the challenges that are associated with working in interdisciplinary research.  What I do find particularly challenging at times is staying on top of the most cutting-edge literature in both the microtechnology and the biology related to my lab’s work.

Shaurya: In vivo biological responses are incredibly complex. The ability to carefully design devices to elucidate systematically the underlying biophysics through in vitro systems requires bringing together various skill sets and intellectual expertise from microfluidic device design, fabrication, and characterization to appropriate biological models followed by subsequent analysis and modeling. Integrating all these skills and expertise to one platform via an interdisciplinary team is both exciting and challenging.

In which upcoming conferences or events may our readers meet you?

Jonathan: My travel patterns have varied from year to year but I typically attend Experimental Biology (or FASEB) because of my involvement with the Microcirculatory Society.  I also typically attend the Summer Biomechanics, Bioengineering, and Biotransport Conference (SB3) and the Biomedical Engineering Society (BMES) Annual Meeting.  I have also enjoyed attending the ASME NanoEngineering for Medicine and Biology (NEMB) conference.  I have not been as active in attending some of the disease specific conferences but intend to start doing so.

Shaurya: Our results are shared at many premier meetings like MicroTAS, Hilton Head Workshop, and other related meetings.

How do you spend your spare time?

Jonathan: My wife is trained as a social worker and is a big proponent of heath and wellness.  Thus, we try to stay active.  For example, we like to take our son biking with us.  He is only 2 years-old now so he is secured to seat on the front of my wife’s bike.  Admittedly, we typically just bike to our favorite local coffee shop.  I have also gotten into a little more extensive cycling, driven largely by my involvement with the OSU Comprehensive Cancer Center Pelotonia, which is an annual philanthropic bike race that has raised over $150 million for cancer research since it was started in 2008.  I have rode in every Pelotonia race since I started at OSU in 2014.

Shaurya:  Family time is essential to my success. Sharing my spare time with an incredibly supportive wife, amazing kids (and a wonderful fur-baby, dog) is time well spent. Any residual time after that is taken up by reading and working in my yard tending to my flower beds and lawn.

 Which profession would you choose if you were not a scientist?

Jonathan: Broadly speaking, probably something in in the business world.  However, if that were the case, I do not think I would be enjoying myself as much as I am now.  Working with my students is probably my favorite part of being an academic scientist.

Shaurya: This is a difficult question as being an engineer and scientist has been not just a profession but a way of life in thinking about solving problems that impact modern society. As a professor, I also enjoy teaching and working with young(er) minds to develop thought processes for solving problems. In my own younger days I was a fair athlete and so being a coach that would allow me to contribute to future generations as a mentor, teacher, and role-model to facilitate positive impact on our world would be an alternate life for me.

Can you share one piece of career-related advice or wisdom with other early career scientists?

Jonathan: Invest in ideas that excite you the most.  Also, when pursuing collaborative projects, try to go for the ones that are both highly significant and mutually beneficial for all parties involved.

Shaurya: Choose and work on problems you truly care about – it shows in how the science is done and technology is developed and all the essential pieces behind impactful work like idea and concept development, writing and reading to compare against state-of-art, and eventually advancing the state-of-art. Therefore, pursuing problems that one is truly passionate about is important.

We are delighted to introduce our latest Lab on a Chip Emerging Investigator, Wilbur Lam!

Wilbur A. Lam, MD, PhD is an Associate Professor of Biomedical Engineering and Pediatrics at the Georgia Institute of Technology and Emory University and has a unique background as a physician-scientist-engineer trained in pediatric hematology/oncology and bioengineering. Dr. Lam’s interdisciplinary laboratory, located at both Emory and Georgia Tech, includes engineers, biologists, biophysicists, chemists and physicians. Our laboratory serves as a unique “one-stop shop” in which we develop in vitro microsystems to study hematologic processes in both health and disease and then immediately bring those technologies to the patient bedside. More specifically, the Lam laboratory’s research interests involve the development and application of microsystems to enable research in pathologic biophysical blood cell interactions that occur in diseases such as sickle cell disease and thrombosis, as well as further translating those systems into novel therapeutics and diagnostic devices.

Read Wilbur’s Emerging Investigator series paper “Probing blood cell mechanics of hematologic processes at the single micron level” and find out more about him in the interview below:

Your recent Emerging Investigator Series paper focuses on probing blood cell mechanics of hematologic processes. How has your research evolved from your first article to this most recent article?

As a bioengineer and a physician specializing in paediatric haematology, my initial goals for our lab were really twofold: 1) to leverage microscale technologies to apply cell mechanics principles towards investigating clinically relevant biologic processes and 2) to convince the medical and clinical haematology fields that physical phenomena such as shear stress and the mechanical properties of the microenvironment can directly mediate the biologic processes of blood cells and pathophysiology of blood diseases such as sickle cell disease and thrombosis. Over the last few years, I think our lab and other groups have accomplished that and we’re now concentrating on not only the basic science questions of blood cell mechanics but how to apply the microtechnologies we develop as potential diagnostics and even therapeutic systems for patients with blood diseases.

What aspect of your work are you most excited about at the moment?

Along those same lines, we’ve been at this game long enough to see some of our microtechnologies translate to my patients with blood diseases, which we find pretty exciting. For example, we just received FDA clearance for a point-of-care anaemia diagnostic our lab developed. We also have several other blood cell mechanics-based microtechnologies that are in our lab’s translational pipeline we’re pretty excited about. For instance, we’ve developed a microfluidic system that can assess platelet contraction forces at the single cell level and we’re now trying to determine whether that system can be used to diagnose patients with bleeding disorders, a clinical interest of mine. At the same time, we’re also trying to leverage that mechanical phenomenon of platelet contraction as a “Trojan Horse” strategy of targeted drug delivery for haemophilia, which we find to be pretty sci-fi and exciting. Moreover, using fairly simple microfluidic devices, we determined that intravenous hydration, a standard first-line therapy for sickle cell disease, may have beneficial as well as deleterious effects on red cell mechanics, which could potentially alter how we treat this disease. We’ve also developed technologies that can enable the translation of other technologies including a microfluidic device that can improve the transduction efficiency of lentiviruses for gene therapy and CAR T-cell therapy, which are both making significant clinical impacts right now. That said, we still remain very interested in the basic science of blood cell mechanics, which is evidenced by this current paper of ours, and we have active projects including but not limited to investigating leukocyte mechanics and are developing new microfluidic strategies to study and model bleeding.

In your opinion, what is the biggest potential impact the results of this research will have on blood disorder diagnostics?

I think impact of our research regarding blood disorder diagnostics can be measured in several ways. First, we obviously want to positively affect and help as many patients and people as possible, which is why we’re clearly excited about the recent FDA 510K clearance of our point-of-care anaemia diagnostic. For that project, we’re currently planning our manufacturing and distribution strategy with different partners to commercialize and disseminate this technology in the US and abroad to impact as many people globally as we can. In addition, we can also measure impact on a more personal level. One of the reasons why our lab has been fortunate enough to be able to recruit the best graduate students and postdoctoral fellows is because of our unique setup in which our lab is located both on the engineering side at Georgia Tech as well as the clinical side at Emory University and Children’s Healthcare of Atlanta, where I am a practicing physician. I’ve truly been blessed to work with the best and most talented students and postdocs in the field of bioengineering and I think they enjoy the fact that they can design a device and literally see it be used on a real live patient within a relatively short time frame. This is great for my patients as well, who are able to witness firsthand how medical technology develops and the potential of how it can improve their own lives in the near future. So, in essence, our lab has developed a “basement-to-bench-to-bedside” approach in which we design and develop microtechnologies to not only study disease but also directly translate these to the patients I care for and even conduct clinical assessments and trials for those devices – all under one roof. By the way, if your readers can help me come up with a better word than “basement” while still maintaining the alliteration as well as the overall message of the phrase, my lab and I will be extremely grateful.

What do you find most challenging about your research?

Like many other bioengineering laboratories among your readership, successful design and development of a novel micro/nanoscale technology is only half the battle. Then you have to do the actual experiment to demonstrate its utility and hope it delivers some type of value. This can be frustrating at times, as our projects can take twice as long as average, but the hope is that our impact will be doubled as well.

In which upcoming conferences or events may our readers meet you?

I attend the annual American Society of Hematology and International Society on Thrombosis and Haemostasis meetings as I serve on the scientific committees for both of them. I also frequently attend the annual Biomedical Engineering Society and MicroTAS meetings as well.

How do you spend your spare time?

I answer interview questions for scientific blogs! Seriously, I’m a huge fan of pop culture and pop music. I even have a lifetime subscription to Rolling Stone, which I’ve been starting to regret in recent years as I’ve grown older as the covers of that magazine have progressively gotten more risqué (or maybe that’s just my perception as whatever semblance of hipness and coolness I ever had is exponentially decreasing with time). I also still pick up my guitar every now and then – especially when I’m procrastinating writing a grant or submitting grades.

Which profession would you choose if you were not a scientist?

I find that when most people are asked this question, they give an idealized answer, so I’ll do the same. I’d like to say that I’d be a successful songwriter/musician as I’ve played guitar in bands from my teenage years until my first faculty position (during my clinical training, I played in an all-paediatrician band named “Booster Shot”). However, to be frank, I really wasn’t that good and seriously doubt I could have made it as a professional musician. So, I think the realistic answer is that my most likely alternative profession would be that of a disgruntled sales associate at a Guitar Center somewhere or working as a roadie for artists a fraction of my age and whom I most likely would have despised. So, it’s good that this science and medicine thing worked out…

Can you share one piece of career-related advice or wisdom with other early career scientists?

Hone your writing skills, start early and keep practicing. I am constantly amazed at how much of my time is devoted to writing and how important that skill is to be a successful scientist. Whether it’s writing or editing papers, lectures, or grants, I find I actually spend most of my time writing. In retrospect, this makes sense as communication really is the currency of science, but there’s no way my younger self would believe me if I were to travel back in time to let him what was ahead of him. I’ve had many young people tell me they want to go into science specifically because they dislike writing, which is obviously a misperception I’m quick to point out. In fact, one joke (and not a very good one, admittedly) I often share with my students is that as a scientist, I actually write really bland non-fiction for a living and for a very small audience, and when I’m grantwriting, I’m only writing to an audience of three people.

We are delighted to introduce our latest Lab on a Chip Emerging Investigator, Pouya Rezai!

Dr. Pouya Rezai is an emerging investigator in the fields of microfluidics and Lab-on-Chips (LoC). He received his PhD in Mechanical Engineering from McMaster University in 2012. Dr. Rezai was an NSERC Visiting Fellow at Public Health Agency of Canada before joining York University in July 2013 as an Assistant Professor. He is the Graduate Program Director of the Department of Mechanical Engineering at York University and the Editor of the Canadian Society for Mechanical Engineering (CSME) bulletin. The overarching goal of his research program is to expand fundamental understanding of the interactions between fluids and nano- to micro-scale biological substances in their micro-environments and to employ this knowledge to devise efficient microsystems for facilitating research and development in human health-related applications

Read Pouya’s Emerging Investigator series paper “A microfluidic device for partial immobilization, chemical exposure and behavioural screening of zebrafish larvae” and find out more about him in the interview below:

Your recent Emerging Investigator Series paper focuses on a microfluidic device to partially immobilise Zebrafish Larvae for behavioural screening. How has your research evolved from your first article to this most recent article?

I started my work on organisms-on-a-chip with the C. elegans worm model. Our work was initially focused on C. elegans response to electric field in microchannels, a phenomenon called electrotaxis. We then became interested in using electrotaxis as a tool to screen movement of worms under exposure to chemicals. Recently, we have become interested in not only electrotaxis, but also chemotaxis of C. elegans and other model organisms such as Drosophila melanogaster and Danio rerio in lab-on-chips. We have developed multiple microfluidic devices for neurobehavioral screening of these organisms. Our goal is to continue working on the same models at the behavioural level but also focus on their cellular responses to stimuli. Our long term objective is to use our organism-on-a-chip devices for drug screening and toxicology studies in collaboration with academia and industry.

What aspect of your work are you most excited about at the moment?

Two major aspects of my work as a professor excites me the most. First and foremost is being able to teach and train young students in the fields of Mechanical and Biomedical Engineering that I am passionate about; and second is having the opportunity to apply my knowledge as an engineer directly to human health related issues. Due to the interdisciplinary nature of our research, I find the collaborative aspects of our work very rewarding for me and my trainees.

In your opinion, what is the biggest benefit of immobilising Zebrafish Larvae for analysis over the conventional droplet-based technique?

The most significant benefit is achieving higher sensitivity in quantifying subtle movement behavioural phenotypes of zebrafish in an easier and faster way. In droplets, you either need an expert to monitor movement manually or complex setups for tracking larvae’s movement in the droplet. With our technique, minimally trained personnel can quickly gain the ability to assay zebrafish movement under exposure to various chemicals.

What do you find most challenging about your research?

We develop devices for live organisms with the capability of making voluntary decisions while in the chip. One does not encounter this challenge with cultured cells or molecules. Decision-making generates opportunities to study sensory-motor responses at the whole-organism level, but also produces a wide variety of challenges in designing microfluidic devices and quantification of the desired biological processes. Another challenge is the general trend in the field to move towards biological models that better mimic human diseases and disorders. This has generated significant momentum towards the use of human-derived cells in biomimetic microfluidic devices. However, I still think there are many unanswered questions that can be addressed by small scale organisms.

In which upcoming conferences or events may our readers meet you?

The International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS) is my favorite conference to go to every year. Some other events that we attend are the MEMS and Transducers conferences.

How do you spend your spare time?

Time is the most precious thing in the world. The nature of an academic job requires a significant dedication of time to professional development, especially at the initial stages of your career. Is this a correct path that we have taken? Let’s not get there for now!
Like many of my colleagues who are my role models and mentors, I rarely have any spare time to be spent on my hobbies. But the most important activity that I enjoy doing, and I wish I could do much more, is to spend quality time with my lovely family. After this, I enjoy nature and listening to good music.

Which profession would you choose if you were not a scientist?

I would pursue the entrepreneurship path and start my own business to help resolve a pressing health related issue.

Can you share one piece of career-related advice or wisdom with other early career scientists?

One of the most influential factors during my professional career has been the opportunity to have excellent mentors and role models who have guided me throughout my postgraduate studies and academic career. The leaders in the field and their path to success have been very inspiring to me in the recent past. I recommend early career scientists to reach out to their communities and seek professional advise on their research and teaching activities.

We are delighted to introduce our latest Lab on a Chip Emerging Investigator – Milad Abolhasani!

Milad Abolhasani is currently an Assistant Professor in the Department of Chemical and Biomolecular Engineering at North Carolina State University. He received his B.Sc. (2008) and M.A.Sc. (2010) degrees in Mechanical Engineering from Sharif University of Technology and the University of British Columbia, respectively. He then obtained his Ph.D. degree (2014) from the Department of Mechanical and Industrial Engineering in collaboration with the Departments of Chemistry and Chemical Engineering at the University of Toronto. Prior to joining NC State University, he was a postdoctoral fellow in the Department of Chemical Engineering at MIT (Jensen group, 2014-2016), where he developed a modular flow chemistry strategy for in-situ mass transfer and kinetic studies of single/multi-phase chemical processes including bi-phasic cross-coupling reactions and colloidal synthesis and ligand exchange of semiconductor nanocrystals. Dr. Abolhasani‘s research interests include the development of microfluidic technologies tailored for solution-phase processing of energy harvesting nanomaterials and for fundamental studies of transport mechanisms involved in CO2 capture, recovery, and utilization in green chemistry (enabled by switchable solvents). Over the course of his doctoral and postdoctoral research, Dr. Abolhasani received numerous fellowships and awards including NSERC Postdoctoral Fellowship, CSME 2014 Best Graduate Student Paper Award, Bert Wasmund Graduate Fellowship in Sustainable Energy Research, and Russell A. Reynolds Graduate Fellowship in Thermodynamics.

Read his Emerging Investigators paper “Automated microfluidic platform for systematic studies of colloidal perovskite nanocrystals: towards continuous nano-manufacturing” and find out more about his research in the interview below:

Your recent Emerging Investigator Series paper focuses on studying colloidal perovskite nanocrystals. How has your research evolved from your first article to this most recent article?

Well, my first research article as a graduate student (published in Lab on a Chip) was focused on the development of an inexpensive approach for rapid determination of thermodynamic characteristics of gas-liquid reactions using an image processing technique. Since then, I’ve expanded my expertise in multi-phase microfluidic systems with a focus on integrated systems with in-situ spectroscopy and/or in-line analytical characterization capabilities for material- and time-efficient studies of various physical/chemical processes. Few examples of such processes include homogenous catalytic reactions, partition coefficient of pharmaceutical compounds, colloidal synthesis of semiconductor nanocrystals, and hydrophilicity switching of switchable solvents. Despite different applications, the common theme among all multi-phase microfluidic technologies that I’ve developed so far has been the focus on realizing the early promise of microfluidics on minimizing the reagents volume used for each experimental condition while maximizing the amount of data obtained. My latest article builds on my experience in integrated microfluidic systems and in-situ spectroscopy techniques to study the effect of early stage mixing times on the optical properties of in-flow synthesized colloidal perovskite nanocrystals.

What aspect of your work are you most excited about at the moment?

Development of microfluidic technologies to contribute towards the next generation of energy-efficient and solution phase-processed photovoltaics.

In your opinion, what is the biggest advantage to using colloidal organic/inorganic metal-halide perovskite nanocrystals for photovoltaics over the current materials?

From materials perspective, hybrid organic/inorganic perovskite nanocrystals are inexpensive and can be manufactured using solution-phase processing techniques. In addition, these shiny nanocrystals possess high surface defect tolerance, high and broad absorption coefficient, high quantum-yield, and long charge carrier lifetime and diffusion length. Combining the superior physicochemical properties of colloidal perovskite nanocrystals with precise band-gap engineering and unparalleled experimental parameter control offered by multi-phase microfluidic platforms make them a promising candidate for the next generation photovoltaics and LED displays.

What do you find most challenging about your research?

Learning about details of different steps involved in manufacturing thin-film solar cells. It is challenging but fascinating to learn.

In which upcoming conferences or events may our readers meet you?

I am currently conducting this interview from MicroTAS 2017 conference in Savannah, GA. I will be attending the Annual AIChE meeting in Minneapolis, MN, between Oct 29 – Nov 3.

How do you spend your spare time?

Catching up with our favorite TV shows (TWD and GOT) with my wife

Which profession would you choose if you were not a scientist?

I would most probably choose to become an architect. I was (and am) always fascinated by “futuristic looking buildings” around the world such as Galaxy Soho in Beijing and Notre Dame du Haut in Ronchamp. The level of attention to details and precision in engineering are just mind-blowing.

Can you share one piece of career-related advice or wisdom with other early career scientists?

In my opinion, focusing on one long-term visionary project that fits your research interests and expertise should be the main goal of a junior faculty. There are so many interesting problems around you, but there is probably only ONE big-impact problem that would truly fit your background which you (hopefully) can solve within your precious pre-tenure adventures.