• As the coronavirus-led economic shutdown drags on, many investors have started counseling startups to have more than a years' worth of "runway" to avoid having to raise funding on poor terms.
• But VCs are split on how much startups should be socking away. Some have estimated 18 months oof reserves could suffice, while others say as much as 3 years' worth of runway is ideal.
• The different time frames depends on the age of the startup along with which industry they operate in. Younger startups typically have fewer overhead expenses, while older startups likely have more employees and pricey office leases.
• Also, those companies that may be able to resume work as essential services may need less cash if they are able to generate revenue.
• VCs are uniformly bracing for an economic slowdown, but the severity of downturn is still up for debate. 
• Click here for more BI Prime stories.

Startups are facing what could become the worst economic downturn in several decades, and VCs are begging them to take drastic measures to improve their chances of making it through. 

Most Americans who lived through the 2008 financial crisis will know that a savings stockpile or rainy day fund can mean the difference between surviving and thriving during tough times, but as recent studies have shown, many tech startups and VC firms don't have a similar first-hand experience; many have only known boom times and are now venturing into uncharted waters.

One thing VCs agree on is that startups need to quickly rein in growth plans — ideally as soon as yesterday — and start scrutinizing expenses. Anything nonessential should be cut or suspended indefinitely, headcount should be reduced, and pricey office leases eliminated if possible, all with the goal of extending a startup's "runway."

In Silicon Valley, runway refers to how much cash a startup has on hand to put against its operating expenses. If, for example, a startup has roughly $100,000 in monthly operating expenses and has $1 million in the bank, they are looking at a 10-month runway, assuming revenue stays roughly flat.

In the days before the coronavirus pandemic, a startup's runway dictated when it had to start looking for additional funding. Instead of cutting expenses, the popular solution was to simply put more VC money in the bank. This helped high flying startups like Uber and Airbnb expand at a breakneck pace — VC dollars kept pouring in and the companies remained unprofitable as they chased growth at all costs.

But now, VCs are saying that's no longer an option. Founders Fund general partner Keith Rabois said on a podcast recently that profitability is now being rewarded much more than high-growth. 

For startups that aren't profitable, that means hunkering down and ensuring there are enough reserves to last through the crisis.

So how long does the runway need to be? 

Many VCs that Business Insider has spoken to are advising their startups to have at least 18 months of runway. But some VCs say startups should have upwards of 3 years' of expenses saved up. 

The length of time can vary depending on the startup, one investor told Business Insider, pointing to the startup's age and industry as important factors. An early-stage company with a handful of employees and low-overhead costs might easily stretch a $500,000 seed check, whereas a growth-stage biotech startup with hundreds of employees, expensive hardware, and pricey office space might struggle to make tens of millions of dollars in funding make it through 12 months. Those that can't cut costs will be forced to fundraise with poor terms and risk the dreaded downround. 

"You can always easily dial back up the aggressiveness and risk profile if we get more optimistic visibility, but if you don't take action right away — to preserve capital, cut your burn rate, have fundamentally attractive unit economics, edit the product to make more sense in the new world order — if you don't do those right away, the opportunity to do those things and survive is probably lost forever," Rabois said in the April Talkshow broadcast.

Rabois is in the camp of pessimists, generally speaking, who think the economic downturn will not only drag on through 2020, but could eventually turn into an economic depression the likes of which could rival the Great Depression of the 1930s. He said that his VC peers are starting to rein in the freewheeling deal-making that has defined the last two decades of the Silicon Valley startup ecosystem, and are now treading cautiously. It's time that startups do the same, he said.

SEE ALSO: Lower valuations and a long wait for funding: Two top early-stage VCs dish on how they are counseling startups to withstand long-term economic uncertainty

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For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.

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